title: Navigating Transcriptional Coregulator Ensembles to Establish Genetic Networks: A GATA Factor Perspective.
abstract: Complex developmental programs require orchestration of intrinsic and extrinsic signals to control cell proliferation, differentiation, and survival. Master regulatory transcription factors are vital components of the machinery that transduce these stimuli into cellular responses. This is exemplified by the GATA family of transcription factors that establish cell type-specific genetic networks and control the development and homeostasis of systems including blood, vascular, adipose, and cardiac. Dysregulated GATA factor activity/expression underlies anemia, immunodeficiency, myelodysplastic syndrome, and leukemia. Parameters governing the capacity of a GATA factor expressed in multiple cell types to generate cell type-specific transcriptomes include selective coregulator usage and target gene-specific chromatin states. As knowledge of GATA-1 mechanisms in erythroid cells constitutes a solid foundation, we will focus predominantly on GATA-1, while highlighting principles that can be extrapolated to other master regulators. GATA-1 interacts with ubiquitous and lineage-restricted transcription factors, chromatin modifying/remodeling enzymes, and other coregulators to activate or repress transcription and to maintain preexisting transcriptional states. Major unresolved issues include: how does a GATA factor selectively utilize diverse coregulators; do distinct epigenetic landscapes and nuclear microenvironments of target genes dictate coregulator requirements; and do gene cohorts controlled by a common coregulator ensemble function in common pathways. This review will consider these issues in the context of GATA factor-regulated hematopoiesis and from a broader perspective.
authors.affiliation: UW-Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States; UW-Madison Blood Research Program, Madison, WI, United States.
authors.forename: A W
authors.initials: AW
authors.lastname: DeVilbiss
authors.affiliation: UW-Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States; UW-Madison Blood Research Program, Madison, WI, United States.
authors.forename: N
authors.initials: N
authors.lastname: Tanimura
authors.affiliation: UW-Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States; UW-Madison Blood Research Program, Madison, WI, United States.
authors.forename: S C
authors.initials: SC
authors.lastname: McIver
authors.affiliation: UW-Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States; UW-Madison Blood Research Program, Madison, WI, United States.
authors.forename: K R
authors.initials: KR
authors.lastname: Katsumura
authors.affiliation: UW-Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States; UW-Madison Blood Research Program, Madison, WI, United States.
authors.forename: K D
authors.initials: KD
authors.lastname: Johnson
authors.affiliation: UW-Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States; UW-Madison Blood Research Program, Madison, WI, United States. Electronic address: ehbresni@wisc.edu.
authors.forename: E H
authors.initials: EH
authors.lastname: Bresnick
mesh_terms: D000818:Animals; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism; D050980:GATA Transcription Factors / Q000235:genetics / Q000378:metabolism*; D053263:Gene Regulatory Networks; D006655:Histone Deacetylases / Q000378:metabolism; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D009707:Nucleosomes / Q000235:genetics / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D050980:GATA Transcription Factors; D009687:Nuclear Proteins; D009707:Nucleosomes; D014157:Transcription Factors; C107310:Zfpm1 protein, mouse; D011495:Histone-Lysine N-Methyltransferase; C470730:KMT5A protein, human; D006655:Histone Deacetylases
keywords: Chromatin; Epigenetics; Erythrocyte; Erythroid; GATA; Hematopoiesis