Year-end Sale % OFF 
Abstract
The hematopoietic GATA factors GATA-1 and GATA-2, which have distinct and overlapping roles to regulate blood cell development, are reciprocally expressed during erythropoiesis. GATA-1 directly represses Gata2 transcription, and reduced GATA-2 synthesis promotes red blood cell development. Gata2 repression involves "GATA switches" in which GATA-1 displaces GATA-2 from Gata2 regulatory regions. We show that extragenic GATA switch sites occupied by GATA-2 associate with as much RNA polymerase II (Pol II) and basal transcription factors as present at the active Gata2 promoters. Pol II bound to GATA switch sites in the active locus was phosphorylated on serine 5 of the carboxyl-terminal domain, indicative of elongation competence. GATA-1-mediated displacement of GATA-2 from GATA switch sites reduced Pol II recruitment to all sites except the far upstream -77-kb region. Surprisingly, TFIIB occupancy persisted at most sites upon repression. These results indicate that GATA-2-bound extragenic regulatory elements recruit Pol II, GATA-1 binding expels Pol II, and despite the persistent TFIIB-chromatin complexes, Pol II recruitment is blocked.
Highlights
During early hematopoiesis, GATA-2 expressed in multipotent hematopoietic precursors maintains proliferation and/or survival [10, 11]
Based on GATA-1-mediated polymerase II (Pol II) recruitment to the -globin locus control region (LCR) and the finding that GATA-1-mediated repression of Gata2 is associated with reduced Pol II at the 1S and 1G promoters [25], we investigated whether Pol II is recruited and dynamically regulated at Gata2 hypersensitive sites (HSs)
Cell Type-specific Pol II Occupancy at Extragenic HSs of the Active Gata2 Locus Is Abrogated upon Repression—GATA switches at the Ϫ77, Ϫ3.9, Ϫ2.8, Ϫ1.8, and ϩ9.5-kb regions of the Gata2 locus result in broad histone deacetylation of the locus and transcriptional repression [25,26,27]
Summary
GATA-2 expressed in multipotent hematopoietic precursors maintains proliferation and/or survival [10, 11]. Cell Type-specific Pol II Occupancy at Extragenic HSs of the Active Gata2 Locus Is Abrogated upon Repression—GATA switches at the Ϫ77, Ϫ3.9, Ϫ2.8, Ϫ1.8, and ϩ9.5-kb regions of the Gata2 locus result in broad histone deacetylation of the locus and transcriptional repression [25,26,27]. Pol II occupied the promoters, the open reading frame, and the four extragenic GATA switch sites (Ϫ77, Ϫ3.9, Ϫ2.8, and Ϫ1.8 kb) at the transcriptionally active Gata2 locus (Fig. 1C).
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
