title: Dynamics of the epigenetic landscape during erythroid differentiation after GATA1 restoration.
abstract: Interplays among lineage-specific nuclear proteins, chromatin modifying enzymes, and the basal transcription machinery govern cellular differentiation, but their dynamics of action and coordination with transcriptional control are not fully understood. Alterations in chromatin structure appear to establish a permissive state for gene activation at some loci, but they play an integral role in activation at other loci. To determine the predominant roles of chromatin states and factor occupancy in directing gene regulation during differentiation, we mapped chromatin accessibility, histone modifications, and nuclear factor occupancy genome-wide during mouse erythroid differentiation dependent on the master regulatory transcription factor GATA1. Notably, despite extensive changes in gene expression, the chromatin state profiles (proportions of a gene in a chromatin state dominated by activating or repressive histone modifications) and accessibility remain largely unchanged during GATA1-induced erythroid differentiation. In contrast, gene induction and repression are strongly associated with changes in patterns of transcription factor occupancy. Our results indicate that during erythroid differentiation, the broad features of chromatin states are established at the stage of lineage commitment, largely independently of GATA1. These determine permissiveness for expression, with subsequent induction or repression mediated by distinctive combinations of transcription factors.
authors.affiliation: Center for Comparative Genomics and Bioinformatics, Pennsylvania State University, University Park, Pennsylvania 16802, USA.
authors.forename: Weisheng
authors.initials: W
authors.lastname: Wu
authors.forename: Yong
authors.initials: Y
authors.lastname: Cheng
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Keller
authors.forename: Jason
authors.initials: J
authors.lastname: Ernst
authors.forename: Swathi Ashok
authors.initials: SA
authors.lastname: Kumar
authors.forename: Tejaswini
authors.initials: T
authors.lastname: Mishra
authors.forename: Christapher
authors.initials: C
authors.lastname: Morrissey
authors.forename: Christine M
authors.initials: CM
authors.lastname: Dorman
authors.forename: Kuan-Bei
authors.initials: KB
authors.lastname: Chen
authors.forename: Daniela
authors.initials: D
authors.lastname: Drautz
authors.forename: Belinda
authors.initials: B
authors.lastname: Giardine
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Shibata
authors.forename: Lingyun
authors.initials: L
authors.lastname: Song
authors.forename: Max
authors.initials: M
authors.lastname: Pimkin
authors.forename: Gregory E
authors.initials: GE
authors.lastname: Crawford
authors.forename: Terrence S
authors.initials: TS
authors.lastname: Furey
authors.forename: Manolis
authors.initials: M
authors.lastname: Kellis
authors.forename: Webb
authors.initials: W
authors.lastname: Miller
authors.forename: James
authors.initials: J
authors.lastname: Taylor
authors.forename: Stephan C
authors.initials: SC
authors.lastname: Schuster
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Francesca
authors.initials: F
authors.lastname: Chiaromonte
authors.forename: Gerd A
authors.initials: GA
authors.lastname: Blobel
authors.forename: Mitchell J
authors.initials: MJ
authors.lastname: Weiss
authors.forename: Ross C
authors.initials: RC
authors.lastname: Hardison
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics*; D002460:Cell Line; D042002:Chromatin Assembly and Disassembly; D047369:Chromatin Immunoprecipitation; D044127:Epigenesis, Genetic; D004920:Erythropoiesis / Q000235:genetics*; D004958:Estradiol / Q000494:pharmacology / Q000502:physiology; D050982:GATA1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D050989:GATA2 Transcription Factor / Q000378:metabolism; D020869:Gene Expression Profiling; D020868:Gene Silencing; D051379:Mice; D015999:Multivariate Analysis; D010447:Peptide Hydrolases / Q000378:metabolism; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004958:Estradiol; D050982:GATA1 Transcription Factor; D050989:GATA2 Transcription Factor; D010447:Peptide Hydrolases; D011518:Proto-Oncogene Proteins; D011960:Receptors, Estrogen; D011994:Recombinant Proteins; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; C494689:Gata1 protein, mouse; C494712:Gata2 protein, mouse; C489366:Tal1 protein, mouse; C021359:histonase