ORCID Profile
0000-0001-5642-5196
Current Organisation
Deakin University
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Publisher: Public Library of Science (PLoS)
Date: 14-12-2017
Publisher: Wiley
Date: 21-06-2020
DOI: 10.1002/AR.24417
Publisher: Elsevier BV
Date: 06-2018
DOI: 10.1016/J.NUMECD.2018.02.019
Abstract: Maternal high fat diets (mHFD) have been associated with an increased offspring cardiovascular risk. Recently we found that the class IIa HDAC-MEF2 pathway regulates gene programs controlling fatty acid oxidation in striated muscle. This same pathway controls hypertrophic responses in the heart. We hypothesized that mHFD is associated with activation of signal controlling class II a HDAC activity and activation of genes involved in fatty acid oxidation and cardiac hypertrophy in offspring. Female Sprague Dawley rats were fed either normal fat diet (12%) or high fat diet (43%) three weeks prior to mating, remaining on diets until study completion. Hearts of postnatal day 1 (PN1) and PN10 pups were collected. Bioenergetics and respiration analyses were performed in neonatal ventricular cardiomyocytes (NVCM). In offspring exposed to mHFD, body weight was increased at PN10 accompanied by increased body fat percentage and blood glucose. Heart weight and heart weight to body weight ratio were increased at PN1 and PN10, and were associated with elevated signalling through the AMPK-class IIa HDAC-MEF2 axis. The expression of the MEF2-regulated hypertrophic markers ANP and BNP were increased as were expression of genes involved in fatty acid oxidation. However this was only accompanied by an increased protein expression of fatty acid oxidation enzymes at PN10. NVCM isolated from these pups exhibited increased glycolysis and an impaired substrate flexibility. Combined, these results suggest that mHFD induces signalling and transcriptional events indicative of reprogrammed cardiac metabolism and of cardiac hypertrophy in Sprague Dawley rat offspring.
Publisher: Wiley
Date: 07-2007
Publisher: Elsevier BV
Date: 2009
DOI: 10.1016/J.BBRC.2009.11.134
Abstract: Oct4, Nanog and Sox2 constitute a core of transcription factors controlling pluripotency. Differentiation and reprogramming studies have unraveled a few epigenetic modifications associated in relation to the expression state of OCT4, NANOG and SOX2. There is, however, no comprehensive map of chromatin states on these genes in human primary cells at different stages of differentiation. We report here a profile of DNA methylation and of 10 histone modifications on regulatory regions of OCT4, NANOG and SOX2 in embryonal carcinoma cells, mesenchymal stem cells and fibroblasts. Bisulfite sequencing reveals correlation between promoter CpG methylation and repression of OCT4, but not NANOG or SOX2, suggesting distinct repression mechanisms. Whereas none of these genes, even when inactive, harbor repressive trimethylated H3K9, CpG hypomethylated NANOG and SOX2, but not CpG methylated OCT4, are enriched in repressive H3K27me3. H3K79me1 and H3K79me3 tend to parallel each other and are linked to repression. Moreover, we highlight an inverse relationship between H3K27me3 occupancy on promoters and H3K36me3 occupancy on coding regions of OCT4, NANOG and SOX2, suggesting a cross-talk between K27 and K36 methylation. Establishment of distinct repression mechanisms for pluripotency-associated genes may constitute a safeguard system to prevent promiscuous reactivation during development or differentiation.
Publisher: Mary Ann Liebert Inc
Date: 08-2010
Abstract: Mesenchymal stem cells (MSCs) can differentiate into multiple mesodermal cell types in vitro however, their differentiation capacity is influenced by their tissue of origin. To what extent epigenetic information on promoters of lineage-specification genes in human progenitors influences transcriptional activation and differentiation potential remains unclear. We produced bisulfite sequencing maps of DNA methylation in adipogenic, myogenic, and endothelial promoters in relation to gene expression and differentiation capacity, and unravel a similarity in DNA methylation profiles between MSCs isolated from human adipose tissue, bone marrow (BM), and muscle. This similarity is irrespective of promoter CpG content. Methylation patterns of MSCs are distinct from those of hematopoietic progenitor cells (HPCs), pluripotent human embryonic stem cells (hESCs), and multipotent hESC-derived mesenchymal cells (MCs). Moreover, in vitro MSC differentiation does not affect lineage-specific promoter methylation states, arguing that these methylation patterns in differentiated cells are already established at the progenitor stage. Further, we find a correlation between lineage-specific promoter hypermethylation and lack of differentiation capacity toward that lineage, but no relationship between weak promoter methylation and capacity of transcriptional activation or differentiation. Thus, only part of the restriction in differentiation capacity of tissue-specific stem cells is programmed by promoter DNA methylation: hypermethylation seems to constitute a barrier to differentiation, however, no or weak methylation has no predictive value for differentiation potential.
Publisher: Elsevier BV
Date: 10-2010
DOI: 10.1016/J.BBRC.2010.09.116
Abstract: Evidence links pluripotency to a gene regulatory network organized by the transcription factors Oct4, Nanog and Sox2. Expression of these genes is controlled by epigenetic modifications on regulatory regions. However, little is known on profiles of trimethylated H3 lysine residues on coding regions of these genes in pluripotent and differentiated cells, and on the interdependence between promoter and exon occupancy of modified H3. Here, we determine how H3K9, H3K27, H3K36 and H3K79 methylation profiles on exons of OCT4, NANOG and SOX2 correlate with expression and promoter occupancy. Expression of OCT4, SOX2 and NANOG in embryonal carcinoma cells is associated with a looser chromatin configuration than mesenchymal progenitors or fibroblasts, determined by H3 occupancy. Promoter H3K27 trimethylation extends into the first exon of repressed OCT4, NANOG and SOX2, while H3K9me3 occupies the first exon of these genes irrespective of expression. Both H3K36me3 and H3K79me3 are enriched on exons of expressed genes, yet with a distinct pattern: H3K36me3 increases towards the 3' end of genes, while H3K79me3 is preferentially enriched on first exons. Down-regulation of the H3K36 methyltransferase SetD2 by siRNA causes global and gene-specific H3K36 demethylation and global H3K27 hypermethylation however it does not affect promoter levels of H3K27me3, suggesting for the genes examined independence of occupancy of H3K27me3 on promoters and H3K36me3 on exons. mRNA levels are however affected, raising the hypothesis of a role of SetD2 on transcription elongation and/or termination.
Publisher: American Society for Cell Biology (ASCB)
Date: 05-2007
Abstract: Analyses of molecular events associated with reprogramming somatic nuclei to pluripotency are scarce. We previously reported the reprogramming of epithelial cells by extract of undifferentiated embryonal carcinoma (EC) cells. We now demonstrate reprogramming of DNA methylation and histone modifications on regulatory regions of the developmentally regulated OCT4 and NANOG genes by exposure of 293T cells to EC cell extract. OCT4 and NANOG are transcriptionally up-regulated and undergo mosaic cytosine-phosphate-guanosine demethylation. OCT4 demethylation occurs as early as week 1, is enhanced by week 2, and is most prominent in the proximal promoter and distal enhancer. Targeted OCT4 and NANOG demethylation does not occur in 293T extract-treated cells. Retinoic acid-mediated differentiation of reprogrammed cells elicits OCT4 promoter remethylation and transcriptional repression. Chromatin immunoprecipitation analyses of lysines K4, K9, and K27 of histone H3 on OCT4 and NANOG indicate that primary chromatin remodeling determinants are acetylation of H3K9 and demethylation of dimethylated H3K9. H3K4 remains di- and trimethylated. Demethylation of trimethylated H3K9 and H3K27 also occurs however, trimethylation seems more stable than dimethylation. We conclude that a central epigenetic reprogramming event is relaxation of chromatin at loci associated with pluripotency to create a conformation compatible with transcriptional activation.
Publisher: MDPI AG
Date: 12-03-2015
DOI: 10.3390/NU7031881
Publisher: Bioscientifica
Date: 07-2013
DOI: 10.1530/REP-12-0526
Abstract: In mice, epiblast cells found both the germ-line and somatic lineages in the developing embryo. These epiblast cells carry epigenetic information from both parents that is required for development and cell function in the fetus and during post-natal life. However, germ cells must establish an epigenetic program that supports totipotency and the configuration of parent-specific epigenetic states in the gametes. To achieve this, the epigenetic information inherited by the primordial germ cells at specification is erased and new epigenetic states are established during development of the male and female germ-lines. Errors in this process can lead to transmission of epimutations through the germ-line, which have the potential to affect development and disease in the parent's progeny. This review discusses epigenetic reprogramming in the germ-line and the transmission of epigenetic information to the following generation.
No related grants have been discovered for Sanna Barrand.