ORCID Profile
0000-0002-8104-718X
Current Organisations
University of New South Wales
,
Garvan Institute of Medical Research
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Publisher: Portland Press Ltd.
Date: 24-09-2019
DOI: 10.1042/EBC20190030
Abstract: DNA methylation involves the addition of a methyl group to the fifth carbon of the pyrimidine cytosine ring (5-methylcytosine, 5mC). 5mC is widespread in vertebrate genomes where it is predominantly found within CpG dinucleotides. In mammals, 5mC participates in long-term silencing processes such as X-chromosome inactivation, genomic imprinting, somatic silencing of germline genes, and silencing of repetitive DNA elements. The evidence for 5mC as a dynamic gene-regulatory mechanism is mostly limited to specific ex les, and is far from being completely understood. Recent work from erse model systems suggests that 5mC might not always act as a dominant repressive mechanism and that hypermethylated promoters and enhancers can be permissive to transcription in vivo and in vitro. In this review, we discuss the links between 5mC and enhancer activity, and evaluate the role of this biochemical mechanism in various biological contexts.
Publisher: Springer US
Date: 2022
DOI: 10.1007/978-1-0716-2140-0_5
Abstract: Whole-genome bisulfite sequencing (WGBS) is currently the gold standard for DNA methylation (5-methylcytosine, 5mC) profiling however, the destructive nature of sodium bisulfite results in DNA fragmentation and subsequent biases in sequencing data. Such issues have led to the development of bisulfite-free methods for 5mC detection. Nanopore sequencing is a long read nondestructive approach that directly analyzes DNA and RNA fragments in real time. Recently, computational tools have been developed that enable base-resolution detection of 5mC from Oxford Nanopore sequencing data. In this chapter, we provide a detailed protocol for preparation, sequencing, read assembly, and analysis of genome-wide 5mC using Nanopore sequencing technologies.
Publisher: Portland Press Ltd.
Date: 22-06-2021
DOI: 10.1042/BST20200695
Abstract: In vertebrates, cytosine-guanine (CpG) dinucleotides are predominantly methylated, with ∼80% of all CpG sites containing 5-methylcytosine (5mC), a repressive mark associated with long-term gene silencing. The exceptions to such a globally hypermethylated state are CpG-rich DNA sequences called CpG islands (CGIs), which are mostly hypomethylated relative to the bulk genome. CGIs overlap promoters from the earliest vertebrates to humans, indicating a concerted evolutionary drive compatible with CGI retention. CGIs are characterised by DNA sequence features that include DNA hypomethylation, elevated CpG and GC content and the presence of transcription factor binding sites. These sequence characteristics are congruous with the recruitment of transcription factors and chromatin modifying enzymes, and transcriptional activation in general. CGIs colocalize with sites of transcriptional initiation in hypermethylated vertebrate genomes, however, a growing body of evidence indicates that CGIs might exert their gene regulatory function in other genomic contexts. In this review, we discuss the erse regulatory features of CGIs, their functional readout, and the evolutionary implications associated with CGI retention in vertebrates and possibly in invertebrates.
Publisher: Cold Spring Harbor Laboratory
Date: 25-05-2023
DOI: 10.1101/2023.05.25.542242
Abstract: DNA methylation (5-methylcytosine, 5mC) is a repressive gene regulatory mark widespread in vertebrate genomes, yet the developmental dynamics in which 5mC patterns are established vary across species. While mammals undergo two rounds of global 5mC erasure, the zebrafish genome exhibits localized maternal-to-paternal 5mC remodeling, in which the sperm epigenome is inherited in the early embryo. To date, it is unclear how evolutionarily conserved such 5mC remodeling strategies are, and what their biological function is. Here, we studied 5mC dynamics during the embryonic development of sea l rey ( Petromyzon marinus ), a jawless vertebrate which occupies a critical phylogenetic position as the sister group of the jawed vertebrates. We employed base-resolution 5mC quantification in the l rey germline, embryonic and somatic tissues, and discovered large-scale maternal-to-paternal epigenome remodeling that affects % of the embryonic genome and is predominantly associated with partially methylated domains (PMDs). We further demonstrate that sequences eliminated during programmed genome rearrangement (PGR), a hallmark of l rey embryogenesis, are hypermethylated in sperm prior to the onset of PGR. Our study thus unveils important insights into the evolutionary origins of vertebrate 5mC reprogramming, and how this process might participate in erse developmental strategies.
Publisher: Proceedings of the National Academy of Sciences
Date: 28-06-2019
Abstract: In hypersaline environments, Nanohaloarchaeota (Diapherotrites, Parvarchaeota, Aenigmarchaeota, Nanoarchaeota, Nanohaloarchaeota [DPANN] superphylum) are thought to be free-living microorganisms. We report cultivation of 2 strains of Antarctic Nanohaloarchaeota and show that they require the haloarchaeon Halorubrum lacusprofundi for growth. By performing growth using enrichments and fluorescence-activated cell sorting, we demonstrated successful cultivation of Candidatus Nanohaloarchaeum antarcticus, purification of Ca. Nha. antarcticus away from other species, and growth and verification of Ca. Nha. antarcticus with Hrr. lacusprofundi these findings are analogous to those required for fulfilling Koch’s postulates. We use fluorescent in situ hybridization and transmission electron microscopy to assess cell structures and interactions metagenomics to characterize enrichment taxa, generate metagenome assembled genomes, and interrogate Antarctic communities and proteomics to assess metabolic pathways and speculate about the roles of certain proteins. Metagenome analysis indicates the presence of a single species, which is endemic to Antarctic hypersaline systems that support the growth of haloarchaea. The presence of unusually large proteins predicted to function in attachment and invasion of hosts plus the absence of key biosynthetic pathways (e.g., lipids) in metagenome assembled genomes of globally distributed Nanohaloarchaeota indicate that all members of the lineage have evolved as symbionts. Our work expands the range of archaeal symbiotic lifestyles and provides a genetically tractable model system for advancing understanding of the factors controlling microbial symbiotic relationships.
No related grants have been discovered for Allegra Angeloni.