ORCID Profile
0000-0002-6441-6529
Current Organisations
University of Western Australia
,
Queen Mary University of London
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Epigenetics (incl. Genome Methylation and Epigenomics) | Genomics | Genetics
Publisher: Springer Science and Business Media LLC
Date: 26-09-2019
Publisher: Oxford University Press (OUP)
Date: 07-2013
DOI: 10.1093/GBE/EVT102
Publisher: Oxford University Press (OUP)
Date: 23-02-2014
DOI: 10.1093/GBE/EVU038
Publisher: Elsevier BV
Date: 10-2019
DOI: 10.1016/J.GDE.2019.07.010
Abstract: Transcription factors (TFs) have a central role in genome regulation directing gene transcription through binding specific DNA sequences. Eukaryotic genomes encode a large ersity of TF classes, each defined by unique DNA-interaction domains. Recent advances in genome sequencing and phylogenetic placement of erse eukaryotic and archaeal species are re-defining the evolutionary history of eukaryotic TFs. The emerging view from a comparative genomics perspective is that the Last Eukaryotic Common Ancestor (LECA) had an extensive repertoire of TFs, most of which represent eukaryotic evolutionary novelties. This burst of TF innovation coincides with the emergence of genomic nuclear segregation and complex chromatin organization.
Publisher: Cold Spring Harbor Laboratory
Date: 19-02-2020
DOI: 10.1101/2020.02.18.954784
Abstract: The genomes of non-bilaterian metazoans are key to understanding the molecular basis of early animal evolution. However, a full comprehension of how animal-specific traits such as nervous systems arose is hindered by the scarcity and fragmented nature of genomes from key taxa, such as Porifera. Ephydatia muelleri is a freshwater sponge found across the northern hemisphere. Here we present its 326 Mb genome, assembled to high contiguity (N50: 9.88 Mb) with 23 chromosomes on 24 scaffolds. Our analyses reveal a metazoan-typical genome architecture, with highly shared synteny across Metazoa, and suggest that adaptation to the extreme temperatures and conditions found in freshwater often involves gene duplication. The pancontinental distribution and ready laboratory culture of E. muelleri make this a highly practical model system, which with RNAseq, DNA methylation and bacterial licon data spanning its development and range allows exploration of genomic changes both within sponges and in early animal evolution.
Publisher: Springer Science and Business Media LLC
Date: 2011
Publisher: Oxford University Press (OUP)
Date: 25-05-2011
Publisher: Springer Science and Business Media LLC
Date: 05-2018
DOI: 10.1038/S41467-018-04260-2
Abstract: The original version of this Article contained an error in the spelling of the author Hongfei Li, which was incorrectly given as Fei Hong. This has now been corrected in both the PDF and HTML versions of the Article.
Publisher: eLife Sciences Publications, Ltd
Date: 04-11-2014
DOI: 10.7554/ELIFE.05218
Abstract: A genetic screen has revealed one of the molecules that allow choanoflagellates, the closest unicellular relative of animals, to form colonies, which could help researchers to answer questions about the earliest days of animal evolution.
Publisher: Springer Science and Business Media LLC
Date: 16-08-2023
DOI: 10.1038/S41586-023-06424-7
Abstract: Cells undergo a major epigenome reconfiguration when reprogrammed to human induced pluripotent stem cells (hiPS cells). However, the epigenomes of hiPS cells and human embryonic stem (hES) cells differ significantly, which affects hiPS cell function 1–8 . These differences include epigenetic memory and aberrations that emerge during reprogramming, for which the mechanisms remain unknown. Here we characterized the persistence and emergence of these epigenetic differences by performing genome-wide DNA methylation profiling throughout primed and naive reprogramming of human somatic cells to hiPS cells. We found that reprogramming-induced epigenetic aberrations emerge midway through primed reprogramming, whereas DNA demethylation begins early in naive reprogramming. Using this knowledge, we developed a transient-naive-treatment (TNT) reprogramming strategy that emulates the embryonic epigenetic reset. We show that the epigenetic memory in hiPS cells is concentrated in cell of origin-dependent repressive chromatin marked by H3K9me3, lamin-B1 and aberrant CpH methylation. TNT reprogramming reconfigures these domains to a hES cell-like state and does not disrupt genomic imprinting. Using an isogenic system, we demonstrate that TNT reprogramming can correct the transposable element overexpression and differential gene expression seen in conventional hiPS cells, and that TNT-reprogrammed hiPS and hES cells show similar differentiation efficiencies. Moreover, TNT reprogramming enhances the differentiation of hiPS cells derived from multiple cell types. Thus, TNT reprogramming corrects epigenetic memory and aberrations, producing hiPS cells that are molecularly and functionally more similar to hES cells than conventional hiPS cells. We foresee TNT reprogramming becoming a new standard for biomedical and therapeutic applications and providing a novel system for studying epigenetic memory.
Publisher: Research Square Platform LLC
Date: 10-04-2023
DOI: 10.21203/RS.3.RS-2774434/V1
Abstract: Whole genome duplications (WGDs) are major events that drastically reshape genome architecture and are causally associated with organismal innovations and radiations 1 . The 2R Hypothesis suggests that two WGD events (1R and 2R) occurred during early vertebrate evolution 2,3 . However, the veracity and timing of the 2R event relative to the ergence of gnathostomes (jawed vertebrates) and cyclostomes (jawless hagfishes and l reys) is unresolved 4-6 and whether these WGD events underlie vertebrate phenotypic ersification remains elusive 7 . Here we present the genome of the inshore hagfish, Eptatretus burgeri . Through comparative analysis with l rey and gnathostome genomes, we reconstruct the early events in cyclostome genome evolution, leveraging insights into the ancestral vertebrate genome. Genome-wide synteny and phylogenetic analyses support a scenario in which 1R occurred in the vertebrate stem-lineage during the early Cambrian, and the 2R event occurred in the gnathostome stem-lineage in the late Cambrian after its ergence from cyclostomes. We find that the genome of stem-cyclostomes experienced two additional, independent genome duplications (herein CR1 and CR2). Functional genomic and morphospace analyses demonstrate that WGD events generally contribute to developmental evolution with similar changes in the regulatory genome of both vertebrate groups. However, appreciable morphological ersification occurred only after the 2R event, questioning the general expectation that WGDs lead to leaps of morphological complexity 7 .
Publisher: Elsevier BV
Date: 09-2015
DOI: 10.1016/J.CUB.2015.07.053
Abstract: The Opisthokonta are a eukaryotic supergroup ided in two main lineages: animals and related protistan taxa, and fungi and their allies [1, 2]. There is a great ersity of lifestyles and morphologies among unicellular opisthokonts, from free-living phagotrophic flagellated bacterivores and filopodiated amoebas to cell-walled osmotrophic parasites and saprotrophs. However, these characteristics do not group into monophyletic assemblages, suggesting r ant convergent evolution within Opisthokonta. To test this hypothesis, we assembled a new phylogenomic dataset via sequencing 12 new strains of protists. Phylogenetic relationships among opisthokonts revealed independent origins of filopodiated amoebas in two lineages, one related to fungi and the other to animals. Moreover, we observed that specialized osmotrophic lifestyles evolved independently in fungi and protistan relatives of animals, indicating convergent evolution. We therefore analyzed the evolution of two key fungal characters in Opisthokonta, the flagellum and chitin synthases. Comparative analyses of the flagellar toolkit showed a previously unnoticed flagellar apparatus in two close relatives of animals, the filasterean Ministeria vibrans and Corallochytrium limacisporum. This implies that at least four different opisthokont lineages secondarily underwent flagellar simplification. Analysis of the evolutionary history of chitin synthases revealed significant expansions in both animals and fungi, and also in the Ichthyosporea and C. limacisporum, a group of cell-walled animal relatives. This indicates that the last opisthokont common ancestor had a complex toolkit of chitin synthases that was differentially retained in extant lineages. Thus, our data provide evidence for convergent evolution of specialized lifestyles in close relatives of animals and fungi from a generalist ancestor.
Publisher: Springer Science and Business Media LLC
Date: 26-02-2016
DOI: 10.1038/SREP21801
Abstract: Inconsistent conclusions have been drawn regarding the phylogenetic age of the Methuselah / Methuselah-like (Mth/Mthl ) gene family of G protein-coupled receptors, the founding member of which regulates development and lifespan in Drosophila . Here we report the results from a targeted homolog search of 39 holozoan genomes and phylogenetic analysis of the conserved seven transmembrane domain. Our findings reveal that the Mth/Mthl gene family is ancient, has experienced numerous extinction and expansion events during metazoan evolution, and acquired the current definition of the Methuselah ectodomain during its exceptional expansion in arthropods. In addition, our findings identify Mthl1 , Mthl5 , Mthl14 , and Mthl15 as the oldest Mth/Mthl gene family paralogs in Drosophila . Future studies of these genes have the potential to define ancestral functions of the Mth/Mthl gene family.
Publisher: eLife Sciences Publications, Ltd
Date: 14-10-2015
DOI: 10.7554/ELIFE.08904
Abstract: Cell-type specification through differential genome regulation is a hallmark of complex multicellularity. However, it remains unclear how this process evolved during the transition from unicellular to multicellular organisms. To address this question, we investigated transcriptional dynamics in the ichthyosporean Creolimax fragrantissima, a relative of animals that undergoes coenocytic development. We find that Creolimax utilizes dynamic regulation of alternative splicing, long inter-genic non-coding RNAs and co-regulated gene modules associated with animal multicellularity in a cell-type specific manner. Moreover, our study suggests that the different cell types of the three closest animal relatives (ichthyosporeans, filastereans and choanoflagellates) are the product of lineage-specific innovations. Additionally, a proteomic survey of the secretome reveals adaptations to a fungal-like lifestyle. In summary, the ersity of cell types among protistan relatives of animals and their complex genome regulation demonstrates that the last unicellular ancestor of animals was already capable of elaborate specification of cell types.
Publisher: Elsevier BV
Date: 03-2020
DOI: 10.1016/J.JMB.2019.11.003
Abstract: Cytosine DNA methylation (5mC) is a widespread base modification in eukaryotic genomes with critical roles in transcriptional regulation. In recent years, our understanding of 5mC has changed because of advances in 5mC detection techniques that allow mapping of this mark on the whole genome scale. Profiling DNA methylomes from organisms across the eukaryotic tree of life has reshaped our views on the evolution of 5mC. In this review, we explore the macroevolution of 5mC in major eukaryotic groups, and then focus on recent advances made in animals. Genomic 5mC patterns as well as the mechanisms of 5mC deposition tend to be evolutionary labile across large phylogenetic distances however, some common patterns are starting to emerge. Within the animal kingdom, 5mC ersity has proven to be much greater than anticipated. For ex le, a previously held common view that genome hypermethylation is a trait exclusive to vertebrates has recently been challenged. Also, data from genome-wide studies are starting to yield insights into the potential roles of 5mC in invertebrate cis regulation. Here we provide an evolutionary perspective of both the well-known and enigmatic roles of 5mC across the eukaryotic tree of life.
Publisher: Springer Science and Business Media LLC
Date: 27-07-2020
DOI: 10.1038/S41467-020-17397-W
Abstract: The genomes of non-bilaterian metazoans are key to understanding the molecular basis of early animal evolution. However, a full comprehension of how animal-specific traits, such as nervous systems, arose is hindered by the scarcity and fragmented nature of genomes from key taxa, such as Porifera. Ephydatia muelleri is a freshwater sponge found across the northern hemisphere. Here, we present its 326 Mb genome, assembled to high contiguity (N50: 9.88 Mb) with 23 chromosomes on 24 scaffolds. Our analyses reveal a metazoan-typical genome architecture, with highly shared synteny across Metazoa, and suggest that adaptation to the extreme temperatures and conditions found in freshwater often involves gene duplication. The pancontinental distribution and ready laboratory culture of E. muelleri make this a highly practical model system which, with RNAseq, DNA methylation and bacterial licon data spanning its development and range, allows exploration of genomic changes both within sponges and in early animal evolution.
Publisher: Cold Spring Harbor Laboratory
Date: 25-06-2019
Abstract: The repressive capacity of cytosine DNA methylation is mediated by recruitment of silencing complexes by methyl-CpG binding domain (MBD) proteins. Despite MBD proteins being associated with silencing, we discovered that a family of arthropod Copia retrotransposons have incorporated a host-derived MBD. We functionally show how retrotransposon-encoded MBDs preferentially bind to CpG-dense methylated regions, which correspond to transposable element regions of the host genome, in the myriapod Strigamia maritima . Consistently, young MBD-encoding Copia retrotransposons (CopiaMBD) accumulate in regions with higher CpG densities than other LTR-retrotransposons also present in the genome. This would suggest that retrotransposons use MBDs to integrate into heterochromatic regions in Strigamia , avoiding potentially harmful insertions into host genes. In contrast, CopiaMBD insertions in the spider Stegodyphus dumicola genome disproportionately accumulate in methylated gene bodies compared with other spider LTR-retrotransposons. Given that transposons are not actively targeted by DNA methylation in the spider genome, this distribution bias would also support a role for MBDs in the integration process. Together, these data show that retrotransposons can co-opt host-derived epigenome readers, potentially harnessing the host epigenome landscape to advantageously tune the retrotransposition process.
Publisher: Springer Science and Business Media LLC
Date: 14-08-2013
DOI: 10.1038/NCOMMS3325
Publisher: Oxford University Press (OUP)
Date: 17-11-2010
Publisher: Cold Spring Harbor Laboratory
Date: 16-08-2017
DOI: 10.1101/170506
Abstract: It is widely assumed that the addition of DNA methylation at CpG rich gene promoters silences gene transcription. However, this conclusion is largely drawn from the observation that promoter DNA methylation inversely correlates with gene expression in natural conditions. The effect of induced DNA methylation on endogenous promoters has yet to be comprehensively assessed. Here, we induced the simultaneous methylation of thousands of promoters in the genome of human cells using an engineered zinc finger-DNMT3A fusion protein, enabling assessment of the effect of forced DNA methylation upon transcription, histone modifications, and DNA methylation persistence after the removal of the fusion protein. We find that DNA methylation is frequently insufficient to transcriptionally repress promoters. Furthermore, DNA methylation deposited at promoter regions associated with H3K4me3 is rapidly erased after removal of the zinc finger-DNMT3A fusion protein. Finally, we demonstrate that induced DNA methylation can exist simultaneously on promoter nucleosomes that possess the active histone modification H3K4me3, or DNA bound by the initiated form of RNA polymerase II. These findings suggest that promoter DNA methylation is not generally sufficient for transcriptional inactivation, with implications for the emerging field of epigenome engineering. Genome-wide epigenomic manipulation of thousands of human promoters reveals that induced promoter DNA methylation is unstable and frequently does not function as a primary instructive biochemical signal for gene silencing and chromatin reconfiguration.
Publisher: Springer Science and Business Media LLC
Date: 04-2010
Abstract: Cell-to-cell communication is a key process in multicellular organisms. In multicellular animals, scaffolding proteins belonging to the family of membrane-associated guanylate kinases (MAGUK) are involved in the regulation and formation of cell junctions. These MAGUK proteins were believed to be exclusive to Metazoa. However, a MAGUK gene was recently identified in an EST survey of Capsaspora owczarzaki , an unicellular organism that branches off near the metazoan clade. To further investigate the evolutionary history of MAGUK, we have undertook a broader search for this gene family using available genomic sequences of different opisthokont taxa. Our survey and phylogenetic analyses show that MAGUK proteins are present not only in Metazoa, but also in the choanoflagellate Monosiga brevicollis and in the protist Capsaspora owczarzaki . However, MAGUKs are absent from fungi, amoebozoans or any other eukaryote. The repertoire of MAGUKs in Placozoa and eumetazoan taxa (Cnidaria + Bilateria) is quite similar, except for one class that is missing in Trichoplax , while Porifera have a simpler MAGUK repertoire. However, Vertebrata have undergone several independent duplications and exhibit two exclusive MAGUK classes. Three different MAGUK types are found in both M. brevicollis and C. owczarzaki: DLG, MPP and MAGI . Furthermore, M. brevicollis has suffered a lineage-specific ersification. The ersification of the MAGUK protein gene family occurred, most probably, prior to the ergence between Metazoa+choanoflagellates and the Capsaspora + Ministeria clade. A MAGI-like, a DLG-like, and a MPP-like ancestral genes were already present in the unicellular ancestor of Metazoa, and new gene members have been incorporated through metazoan evolution within two major periods, one before the sponge-eumetazoan split and another within the vertebrate lineage. Moreover, choanoflagellates have suffered an independent MAGUK ersification. This study highlights the importance of generating enough genome data from the broadest possible taxonomic s ling, in order to fully understand the evolutionary history of major protein gene families.
Publisher: eLife Sciences Publications, Ltd
Date: 2015
Publisher: Elsevier BV
Date: 10-2022
Publisher: Cold Spring Harbor Laboratory
Date: 14-05-2020
DOI: 10.1101/2020.05.13.093203
Abstract: In vertebrates, DNA methylation predominantly occurs at CG dinucleotides even though widespread non-CG methylation (mCH) has been reported in mammalian embryonic and neural cells. Unlike in mammals, where mCH is found enriched at CAC/G trinucleotides and is tissue-restricted, we find that zebrafish embryos as well as adult somatic and germline tissues display robust methylation enrichment at TGCT positions associated with mosaic satellite repeats. These repeats reside in H3K9me3-marked heterochromatin and display mCH reprogramming coincident with zygotic genome activation. Altogether, this work provides insight into a novel form of vertebrate mCH and highlights the substrate ersity of vertebrate DNA methyltransferases.
Publisher: Springer Science and Business Media LLC
Date: 09-04-2018
DOI: 10.1038/S41467-018-03724-9
Abstract: Transposable elements are in a constant arms race with the silencing mechanisms of their host genomes. One silencing mechanism commonly used by many eukaryotes is dependent on cytosine methylation, a covalent modification of DNA deposited by C5 cytosine methyltransferases (DNMTs). Here, we report how two distantly related eukaryotic lineages, dinoflagellates and charophytes, have independently incorporated DNMTs into the coding regions of distinct retrotransposon classes. Concomitantly, we show that dinoflagellates of the genus Symbiodinium have evolved cytosine methylation patterns unlike any other eukaryote, with most of the genome methylated at CG dinucleotides. Finally, we demonstrate the ability of retrotransposon DNMTs to methylate CGs de novo, suggesting that retrotransposons could self-methylate retrotranscribed DNA. Together, this is an ex le of how retrotransposons incorporate host-derived genes involved in DNA methylation. In some cases, this event could have implications for the composition and regulation of the host epigenomic environment.
Publisher: The Company of Biologists
Date: 12-2020
DOI: 10.1242/DEV.192575
Abstract: Almost all animals undergo embryonic development, going from a single-celled zygote to a complex multicellular adult. We know that the patterning and morphogenetic processes involved in development are deeply conserved within the animal kingdom. However, the origins of these developmental processes are just beginning to be unveiled. Here, we focus on how the protist lineages sister to animals are reshaping our view of animal development. Most intriguingly, many of these protistan lineages display transient multicellular structures, which are governed by similar morphogenetic and gene regulatory processes as animal development. We discuss here two potential alternative scenarios to explain the origin of animal embryonic development: either it originated concomitantly at the onset of animals or it evolved from morphogenetic processes already present in their unicellular ancestors. We propose that an integrative study of several unicellular taxa closely related to animals will allow a more refined picture of how the last common ancestor of animals underwent embryonic development.
Publisher: Cold Spring Harbor Laboratory
Date: 08-04-2023
DOI: 10.1101/2023.04.08.536076
Abstract: Whole genome duplications (WGDs) are major events that drastically reshape genome architecture and are causally associated with organismal innovations and radiations 1 . The 2R Hypothesis suggests that two WGD events (1R and 2R) occurred during early vertebrate evolution 2, 3 . However, the veracity and timing of the 2R event relative to the ergence of gnathostomes (jawed vertebrates) and cyclostomes (jawless hagfishes and l reys) is unresolved 4–6 and whether these WGD events underlie vertebrate phenotypic ersification remains elusive 7 . Here we present the genome of the inshore hagfish, Eptatretus burgeri . Through comparative analysis with l rey and gnathostome genomes, we reconstruct the early events in cyclostome genome evolution, leveraging insights into the ancestral vertebrate genome. Genome-wide synteny and phylogenetic analyses support a scenario in which 1R occurred in the vertebrate stem-lineage during the early Cambrian, and the 2R event occurred in the gnathostome stem-lineage in the late Cambrian after its ergence from cyclostomes. We find that the genome of stem-cyclostomes experienced two additional, independent genome duplications (herein CR1 and CR2). Functional genomic and morphospace analyses demonstrate that WGD events generally contribute to developmental evolution with similar changes in the regulatory genome of both vertebrate groups. However, appreciable morphological ersification occurred only after the 2R event, questioning the general expectation that WGDs lead to leaps of morphological complexity 7 .
Publisher: Proceedings of the National Academy of Sciences
Date: 25-11-2013
Abstract: Independent transitions to multicellularity in eukaryotes involved the evolution of complex transcriptional regulation toolkits to control cell differentiation. By using comparative genomics, we show that plants and animals required richer transcriptional machineries compared with other eukaryotic multicellular lineages. We suggest this is due to their orchestrated embryonic development. Moreover, our analysis of transcription factor (TF) expression patterns during the development of animals reveal links between TF evolution, species ontogeny, and the phylotypic stage.
Publisher: Springer Science and Business Media LLC
Date: 28-10-2020
Publisher: American Association for the Advancement of Science (AAAS)
Date: 05-2012
DOI: 10.1126/SCISIGNAL.2002733
Abstract: A genomic survey suggests that cytoplasmic tyrosine kinases ersified before the establishment of multicellular organisms.
Publisher: Oxford University Press (OUP)
Date: 09-12-2013
DOI: 10.1093/JXB/ERT411
Publisher: Springer Netherlands
Date: 2015
Publisher: Elsevier BV
Date: 12-2017
DOI: 10.1016/J.STEM.2017.11.007
Abstract: Somatic cell reprogramming into induced pluripotent stem cells (iPSCs) induces changes in genome architecture reflective of the embryonic stem cell (ESC) state. However, only a small minority of cells typically transition to pluripotency, which has limited our understanding of the process. Here, we characterize the DNA regulatory landscape during reprogramming by time-course profiling of isolated sub-populations of intermediates poised to become iPSCs. Widespread reconfiguration of chromatin states and transcription factor (TF) occupancy occurs early during reprogramming, and cells that fail to reprogram partially retain their original chromatin states. A second wave of reconfiguration occurs just prior to pluripotency acquisition, where a majority of early changes revert to the somatic cell state and many of the changes that define the pluripotent state become established. Our comprehensive characterization of reprogramming-associated molecular changes broadens our understanding of this process and sheds light on how TFs access and change the chromatin during cell-fate transitions.
Publisher: Springer Science and Business Media LLC
Date: 26-05-2020
DOI: 10.1038/S41467-020-16284-8
Abstract: The evolution of winged insects revolutionized terrestrial ecosystems and led to the largest animal radiation on Earth. However, we still have an incomplete picture of the genomic changes that underlay this ersification. Mayflies, as one of the sister groups of all other winged insects, are key to understanding this radiation. Here, we describe the genome of the mayfly Cloeon dipterum and its gene expression throughout its aquatic and aerial life cycle and specific organs. We discover an expansion of odorant-binding-protein genes, some expressed specifically in breathing gills of aquatic nymphs, suggesting a novel sensory role for this organ. In contrast, flying adults use an enlarged opsin set in a sexually dimorphic manner, with some expressed only in males. Finally, we identify a set of wing-associated genes deeply conserved in the pterygote insects and find transcriptomic similarities between gills and wings, suggesting a common genetic program. Globally, this comprehensive genomic and transcriptomic study uncovers the genetic basis of key evolutionary adaptations in mayflies and winged insects.
Publisher: Springer Science and Business Media LLC
Date: 18-01-2021
Publisher: Springer Science and Business Media LLC
Date: 26-07-2022
DOI: 10.1186/S13059-022-02728-5
Abstract: Cytosine DNA methylation is widely described as a transcriptional repressive mark with the capacity to silence promoters. Epigenome engineering techniques enable direct testing of the effect of induced DNA methylation on endogenous promoters however, the downstream effects have not yet been comprehensively assessed. Here, we simultaneously induce methylation at thousands of promoters in human cells using an engineered zinc finger-DNMT3A fusion protein, enabling us to test the effect of forced DNA methylation upon transcription, chromatin accessibility, histone modifications, and DNA methylation persistence after the removal of the fusion protein. We find that transcriptional responses to DNA methylation are highly context-specific, including lack of repression, as well as cases of increased gene expression, which appears to be driven by the eviction of methyl-sensitive transcriptional repressors. Furthermore, we find that some regulatory networks can override DNA methylation and that promoter methylation can cause alternative promoter usage. DNA methylation deposited at promoter and distal regulatory regions is rapidly erased after removal of the zinc finger-DNMT3A fusion protein, in a process combining passive and TET-mediated demethylation. Finally, we demonstrate that induced DNA methylation can exist simultaneously on promoter nucleosomes that possess the active histone modification H3K4me3, or DNA bound by the initiated form of RNA polymerase II. These findings have important implications for epigenome engineering and demonstrate that the response of promoters to DNA methylation is more complex than previously appreciated.
Publisher: Proceedings of the National Academy of Sciences
Date: 22-02-2016
Abstract: An unusual molecule is found in rocks ∼650–540 million y old, and its likely precursor, 24-isopropylcholesterol (24-ipc), is produced by some modern sea sponges. The sterane hydrocarbon analog of 24-ipc offers a potential “molecular fossil” for early animals, but certain algae also produce traces of this molecule, so it is unclear when and how frequently the ability to synthesize 24-ipc evolved. In this study, we connect 24-ipc production to a gene and conclude that algae and sponges independently evolved 24-ipc synthesis through unique gene duplication events. Although the timing of the sponge gene duplication overlaps with the geological record of the molecular fossil, the algal gene duplication occurs significantly later, supporting the connection of 24-ipc to sponges and providing the oldest evidence for animal life.
Publisher: Springer Science and Business Media LLC
Date: 11-12-2020
Location: United Kingdom of Great Britain and Northern Ireland
Start Date: 2014
End Date: 2016
Funder: European Molecular Biology Organization
View Funded ActivityStart Date: 2017
End Date: 2017
Funder: University of Western Australia
View Funded ActivityStart Date: 2021
End Date: 2026
Funder: European Research Council
View Funded ActivityStart Date: 2022
End Date: 12-2024
Amount: $568,152.00
Funder: Australian Research Council
View Funded Activity