@article {112, title = {Dynamics of cardiomyocyte transcriptome and chromatin landscape demarcates key events of heart development.}, journal = {Genome Res}, volume = {29}, year = {2019}, month = {2019 03}, pages = {506-519}, abstract = {

Organogenesis involves dynamic regulation of gene transcription and complex multipathway interactions. Despite our knowledge of key factors regulating various steps of heart morphogenesis, considerable challenges in understanding its mechanism still exist because little is known about their downstream targets and interactive regulatory network. To better understand transcriptional regulatory mechanism driving heart development and the consequences of its disruption in vivo, we performed time-series analyses of the transcriptome and genome-wide chromatin accessibility in isolated cardiomyocytes (CMs) from wild-type zebrafish embryos at developmental stages corresponding to heart tube morphogenesis, looping, and maturation. We identified genetic regulatory modules driving crucial events of heart development that contained key cardiac TFs and are associated with open chromatin regions enriched for DNA sequence motifs belonging to the family of the corresponding TFs. Loss of function of cardiac TFs Gata5, Tbx5a, and Hand2 affected the cardiac regulatory networks and caused global changes in chromatin accessibility profile, indicating their role in heart development. Among regions with differential chromatin accessibility in mutants were highly conserved noncoding elements that represent putative enhancers driving heart development. The most prominent gene expression changes, which correlated with chromatin accessibility modifications within their proximal promoter regions, occurred between heart tube morphogenesis and looping, and were associated with metabolic shift and hematopoietic/cardiac fate switch during CM maturation. Our results revealed the dynamic regulatory landscape throughout heart development and identified interactive molecular networks driving key events of heart morphogenesis.

}, keywords = {Animals, Cells, Cultured, Chromatin, Chromatin Assembly and Disassembly, Gene Expression Regulation, Developmental, Gene Regulatory Networks, Heart, Myocytes, Cardiac, Transcription Factors, Transcriptome, Zebrafish, Zebrafish Proteins}, issn = {1549-5469}, doi = {10.1101/gr.244491.118}, author = {Pawlak, Michal and Kedzierska, Katarzyna Z and Migdal, Maciej and Nahia, Karim Abu and Ramilowski, Jordan A and Bugajski, Lukasz and Hashimoto, Kosuke and Marconi, Aleksandra and Piwocka, Katarzyna and Carninci, Piero and Winata, Cecilia L} } @article {34, title = {Prepatterning of developmental gene expression by modified histones before zygotic genome activation.}, journal = {Dev Cell}, volume = {21}, year = {2011}, month = {2011 Dec 13}, pages = {993-1004}, abstract = {

A hallmark of anamniote vertebrate development is a window of embryonic transcription-independent cell divisions before onset of zygotic genome activation (ZGA). Chromatin determinants of ZGA are unexplored; however, marking of developmental genes by modified histones in sperm suggests a predictive role of histone marks for ZGA. In zebrafish, pre-ZGA development for ten cell cycles provides an opportunity to examine whether genomic enrichment in modified histones is present before initiation of transcription. By profiling histone H3 trimethylation on all zebrafish promoters before and after ZGA, we demonstrate here an epigenetic prepatterning of developmental gene expression. This involves pre-ZGA marking of transcriptionally inactive genes involved in homeostatic and developmental regulation by permissive H3K4me3 with or without repressive H3K9me3 or H3K27me3. Our data suggest that histone modifications are instructive for the developmental gene expression program.

}, keywords = {Animals, Body Patterning, Chromatin, Epigenesis, Genetic, Female, Gene Expression Regulation, Developmental, Histones, Male, Methylation, Multigene Family, Promoter Regions, Genetic, Spermatozoa, Zebrafish, Zebrafish Proteins}, issn = {1878-1551}, doi = {10.1016/j.devcel.2011.10.008}, author = {Lindeman, Leif C and Andersen, Ingrid S and Reiner, Andrew H and Li, Nan and Aanes, H{\r a}vard and {\O}strup, Olga and Winata, Cecilia L and Mathavan, Sinnakaruppan and M{\"u}ller, Ferenc and Alestr{\"o}m, Peter and Collas, Philippe} } @article {69, title = {Chromatin states of developmentally-regulated genes revealed by DNA and histone methylation patterns in zebrafish embryos.}, journal = {Int J Dev Biol}, volume = {54}, year = {2010}, month = {2010}, pages = {803-13}, abstract = {

Embryo development proceeds from a cascade of gene activation and repression events controlled by epigenetic modifications of DNA and histones. Little is known about epigenetic states in the developing zebrafish, despite its importance as a model organism. We report here DNA methylation and histone modification profiles of promoters of developmentally-regulated genes (pou5f1, sox2, sox3, klf4, nnr, otx1b, nes, vasa), as well as tert and bactin2, in zebrafish embryos at the mid-late blastula transition, shortly after embryonic genome activation. We identify four classes of promoters based on the following profiles: (i) those enriched in marks of active genes (H3K9ac, H4ac, H3K4me3) without transcriptionally repressing H3K9me3 or H3K27me3; (ii) those enriched in H3K9ac, H4ac and H3K27me3, without H3K9me3; one such gene was klf4, shown by in situ hybridization to be mosaically expressed, likely accounting for the detection of both activating and repressive marks on its promoter; (iii) those enriched in H3K4me3 and H3K27me3 without acetylation; and (iv) those enriched in all histone modifications examined. Culture of embryo-derived cells under differentiation conditions leads to H3K9 and H4 deacetylation and H3K9 and H3K27 trimethylation on genes that are inactivated, yielding an epigenetic profile similar to those of fibroblasts or muscle. All promoters however retain H3K4me3, indicating an uncoupling of H3K4me3 occupancy and gene expression. All non-CpG island developmentally-regulated promoters are DNA unmethylated in embryos, but hypermethylated in fibroblasts. Our results suggest that differentially expressed embryonic genes are regulated by various patterns of histone modifications on unmethylated DNA, which create a developmentally permissive chromatin state.

}, keywords = {Animals, Blastula, Cell Line, Chromatin, Chromatin Immunoprecipitation, CpG Islands, DNA Methylation, Embryo, Nonmammalian, Fibroblasts, Gene Expression Profiling, Gene Expression Regulation, Developmental, Histones, In Situ Hybridization, Lysine, Methylation, Oligonucleotide Array Sequence Analysis, Promoter Regions, Genetic, Reverse Transcriptase Polymerase Chain Reaction, Zebrafish, Zebrafish Proteins}, issn = {1696-3547}, doi = {10.1387/ijdb.103081ll}, author = {Lindeman, Leif C and Winata, Cecilia L and Aanes, Hvard and Mathavan, Sinnakaruppan and Alestrom, Peter and Collas, Philippe} }