期刊
IUBMB LIFE
卷 72, 期 1, 页码 27-38出版社
WILEY
DOI: 10.1002/iub.2195
关键词
epigenomes; erythropoiesis; gene regulation; genome segmentation; hematopoiesis; integrative analysis; regulatory elements
资金
- National Cancer Institute [R01CA178393]
- National Institute of Diabetes and Digestive and Kidney Diseases [R01DK054937, R24DK106766]
- National Institute of General Medical Sciences [R01GM121613]
- MRC [MC_U137961144, G1000801, MC_U137961145, MC_UU_00016/4, MC_UU_12009/4] Funding Source: UKRI
- NATIONAL HUMAN GENOME RESEARCH INSTITUTE [ZIAHG000083] Funding Source: NIH RePORTER
Members of the GATA family of transcription factors play key roles in the differentiation of specific cell lineages by regulating the expression of target genes. Three GATA factors play distinct roles in hematopoietic differentiation. In order to better understand how these GATA factors function to regulate genes throughout the genome, we are studying the epigenomic and transcriptional landscapes of hematopoietic cells in a model-driven, integrative fashion. We have formed the collaborative multi-lab VISION project to conduct ValI-dated Systematic IntegratiON of epigenomic data in mouse and human hema-topoiesis. The epigenomic data included nuclease accessibility in chromatin, CTCF occupancy, and histone H3 modifications for 20 cell types covering hematopoietic stem cells, multilineage progenitor cells, and mature cells across the blood cell lineages of mouse. The analysis used the Integrative and Discriminative Epigenome Annotation System (IDEAS), which learns all common combinations of features (epigenetic states) simultaneously in two dimensions-along chromosomes and across cell types. The result is a segmentation that effectively paints the regulatory landscape in readily interpretable views, revealing constitutively active or silent loci as well as the loci specifically induced or repressed in each stage and lineage. Nuclease accessible DNA segments in active chromatin states were designated candidate cis-regulatory elements in each cell type, providing one of the most comprehensive registries of candidate hematopoietic regulatory elements to date. Applications of VISION resources are illustrated for the regulation of genes encoding GATA1, GATA2, GATA3, and Ikaros. VISION resources are freely available from our website http://usevision.org.
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