title: The Hematopoietic Stem and Progenitor Cell Cistrome: GATA Factor-Dependent cis-Regulatory Mechanisms.
abstract: Transcriptional regulators mediate the genesis and function of the hematopoietic system by binding complex ensembles of cis-regulatory elements to establish genetic networks. While thousands to millions of any given cis-element resides in a genome, how transcriptional regulators select these sites and how site attributes dictate functional output is not well understood. An instructive system to address this problem involves the GATA family of transcription factors that control vital developmental and physiological processes and are linked to multiple human pathologies. Although GATA factors bind DNA motifs harboring the sequence GATA, only a very small subset of these abundant motifs are occupied in genomes. Mechanistic studies revealed a unique configuration of a GATA factor-regulated cis-element consisting of an E-box and a downstream GATA motif separated by a short DNA spacer. GATA-1- or GATA-2-containing multiprotein complexes at these composite elements control transcription of genes critical for hematopoietic stem cell emergence in the mammalian embryo, hematopoietic progenitor cell regulation, and erythroid cell maturation. Other constituents of the complex include the basic helix-loop-loop transcription factor Scl/TAL1, its heterodimeric partner E2A, and the Lim domain proteins LMO2 and LDB1. This chapter reviews the structure/function of E-box-GATA composite cis-elements, which collectively constitute an important sector of the hematopoietic stem and progenitor cell cistrome.
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 J
authors.initials: KJ
authors.lastname: Hewitt
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.
authors.forename: X
authors.initials: X
authors.lastname: Gao
authors.affiliation: University of Wisconsin School of Medicine and Public Health, Madison, WI, United States.
authors.forename: S
authors.initials: S
authors.lastname: Keles
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: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly; D004247:DNA / Q000378:metabolism; D004277:DNA, Single-Stranded / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D050980:GATA Transcription Factors / Q000235:genetics / Q000378:metabolism*; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D060588:LIM Domain Proteins / Q000235:genetics / Q000378:metabolism; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051792:Basic Helix-Loop-Helix Proteins; D002843:Chromatin; D004247:DNA; D004277:DNA, Single-Stranded; D004268:DNA-Binding Proteins; D050980:GATA Transcription Factors; D051741:Kruppel-Like Transcription Factors; D060588:LIM Domain Proteins; D046912:Multiprotein Complexes; D011518:Proto-Oncogene Proteins; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors; C486312:LDB1 protein, human; C085117:LMO2 protein, human; C080774:erythroid Kruppel-like factor; C067143:TAL1 protein, human
keywords: Cistrome; Composite element; Enhancers; GATA factor; cis-Elements