The Hematopoietic Stem and Progenitor Cell Cistrome: GATA Factor-Dependent cis-Regulatory Mechanisms

K. J. Hewitt, K. D. Johnson, X. Gao, S. Keles, E. H. Bresnick

Research output: Chapter in Book/Report/Conference proceedingChapter

8 Scopus citations

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.

Original languageEnglish (US)
Title of host publicationHematopoiesis, 2016
EditorsEmery H. Bresnick
PublisherAcademic Press Inc.
Pages45-76
Number of pages32
ISBN (Print)9780128033197
DOIs
StatePublished - 2016

Publication series

NameCurrent Topics in Developmental Biology
Volume118
ISSN (Print)0070-2153

Keywords

  • Cistrome
  • Composite element
  • Enhancers
  • GATA factor
  • cis-Elements

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

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    Hewitt, K. J., Johnson, K. D., Gao, X., Keles, S., & Bresnick, E. H. (2016). The Hematopoietic Stem and Progenitor Cell Cistrome: GATA Factor-Dependent cis-Regulatory Mechanisms. In E. H. Bresnick (Ed.), Hematopoiesis, 2016 (pp. 45-76). (Current Topics in Developmental Biology; Vol. 118). Academic Press Inc.. https://doi.org/10.1016/bs.ctdb.2016.01.002