SCL and associated proteins distinguish active from repressive GATA transcription factor complexes

Tamara Tripic, Wulan Deng, Yong Cheng, Ying Zhang, Christopher R. Vakoc, Gregory D. Gregory, Ross C. Hardison, Gerd A. Blobel

Research output: Contribution to journalArticle

137 Scopus citations

Abstract

GATA-1 controls hematopoietic development by activating and repressing gene transcription, yet the in vivo mechanisms that specify these opposite activities are unknown. By examining the composition of GATA-1-associated protein complexes in a conditional erythroid rescue system as well as through the use of tiling arrays we detected the SCL/TAL1, LMO2, Ldbl, E2A complex at all positively acting GATA-1-bound elements examined. Similarly, the SCL complex is present at all activating GATA elements in megakaryocytes and mast cells. In striking contrast, at sites where GATA-1 functions as a repressor, the SCL complex is depleted. A DNA-binding defective form of SCL maintains association with a subset of active GATA elements indicating that GATA-1 is a key determinant for SCL recruitment. Knockdown of LMO2 selectively impairs activation but not repression by GATA-1. ETO-2, an SCL-associated protein with the potential for transcription repression, is also absent from GATA-1-repressed genes but, unlike SCL, fails to accumulate at GATA-1-activated genes. Together, these studies identify the SCL complex as a critical and consistent determinant of positive GATA-1 activity in multiple GATA-1-regulated hematopoietic cell lineages.

Original languageEnglish (US)
Pages (from-to)2191-2201
Number of pages11
JournalBlood
Volume113
Issue number10
DOIs
StatePublished - Mar 5 2009

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