Skip to main page content
U.S. flag

An official website of the United States government

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2016:118:45-76.
doi: 10.1016/bs.ctdb.2016.01.002. Epub 2016 Feb 26.

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

K J Hewitt  1 , K D Johnson  1 , X Gao  1 , S Keles  2 , E H Bresnick  3
Affiliations
Review

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

K J Hewitt et al. Curr Top Dev Biol. 2016.

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.

Keywords: Cistrome; Composite element; Enhancers; GATA factor; cis-Elements.

PubMed Disclaimer

Figures

Figure 1 -
Figure 1 -
Composite E-box-GATA elements regulate diverse aspects of hematopoietic stem/progenitor cell development and function. A multimeric complex, consisting of GATA-2, Scl/TAL-1, E2A, Lmo2, and LDB1, and likely additional components, forms at a highly restricted subset of E-box-GATA elements in the genome. The GATA-2-activated E-box-GATA elements are important constituents of the HSPC cistrome, which orchestrates vital steps in the stem and progenitor cell transitions that give rise to the full complement of blood cells. Examples of genes controlled by GATA-2 through these elements include Gata2, Samd14, Epb4.2, Bcl2l1, and Dapp1.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Anderson KP, Crable SC, Lingrel JB, 1998. Multiple proteins binding to a GATA-E box-GATA motif regulate the erythroid Kruppel-like factor (EKLF) gene. J. Biol. Chem 273, 14347–14354. - PubMed
    1. Anderson KP, Crable SC, Lingrel JB, 2000. The GATA-E-box motif in the EKLF promoter is required for in vivo expression. Blood 95, 1652–1655. - PubMed
    1. Aplan PD, Lombardi DP, Reaman GH, Sather HN, Hammond GD, Kirsch IR, 1992a. Involvement of the putative hematopoietic transcription factor SCL in T-cell acute lymphoblastic leukemia. Blood 79, 1327–1333. - PubMed
    1. Aplan PD, Nakahara K, Orkin SH, Kirsch IR, 1992b. The SCL gene product: a positive regulator of erythroid differentiation. EMBO J. 11, 4073–4081. - PMC - PubMed
    1. Aplan PD, Raimondi SC, Kirsch IR, 1992c. Disruption of the SCL gene by a t(1;3) translocation in a patient with T cell acute lymphoblastic leukemia. J. Exp. Med 176, 1303–1310. - PMC - PubMed

MeSH terms