@article{225f192fc77246a68e0ffc008268cbfb,
title = "Systematic integration of GATA transcription factors and epigenomes via IDEAS paints the regulatory landscape of hematopoietic cells",
abstract = "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 ValIdated Systematic IntegratiON of epigenomic data in mouse and human hematopoiesis. 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.",
keywords = "epigenomes, erythropoiesis, gene regulation, genome segmentation, hematopoiesis, integrative analysis, regulatory elements",
author = "Hardison, {Ross C.} and Yu Zhang and Keller, {Cheryl A.} and Guanjue Xiang and Heuston, {Elisabeth F.} and Lin An and Jens Lichtenberg and Giardine, {Belinda M.} and David Bodine and Shaun Mahony and Qunhua Li and Feng Yue and Weiss, {Mitchell J.} and Blobel, {Gerd A.} and James Taylor and Jim Hughes and Higgs, {Douglas R.} and Berthold G{\"o}ttgens",
note = "Funding Information: 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 V al I dated S ystematic I ntegrati ON of epigenomic data in mouse and human hematopoiesis. 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 I ntegrative and D iscriminative E pigenome A nnotation S ystem (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. Funding information National Cancer Institute, Grant/Award Number: R01CA178393; National Institute of Diabetes and Digestive and Kidney Diseases, Grant/Award Numbers: R01DK054937, R24DK106766; National Institute of General Medical Sciences, Grant/Award Number: R01GM121613 Funding Information: The VISION project is supported by a grant from NIH/NIDDK R24DK106766 (multi-PI). Additional support of this work is from NIH/GM R01GM121613 (to Y.Z. and S.M.), NIH/NIDDK R01DK054937 (to G.B.), and NIH/NCI R01CA178393 (to R.H.). Funding Information: The VISION project is supported by a grant from NIH/NIDDK R24DK106766 (multi‐PI). Additional support of this work is from NIH/GM R01GM121613 (to Y.Z. and S.M.), NIH/NIDDK R01DK054937 (to G.B.), and NIH/NCI R01CA178393 (to R.H.). Publisher Copyright: {\textcopyright} 2019 The Authors. IUBMB Life published by Wiley Periodicals, Inc. on behalf of International Union of Biochemistry and Molecular Biology.",
year = "2020",
month = jan,
day = "1",
doi = "10.1002/iub.2195",
language = "English (US)",
volume = "72",
pages = "27--38",
journal = "IUBMB Life",
issn = "1521-6543",
publisher = "Wiley-Blackwell",
number = "1",
}