| |
|
|
|
|
|
|
|||
|
Blood, 5 March 2009, Vol. 113, No. 10, pp. 2191-2201. Prepublished online as a Blood First Edition Paper on November 14, 2008; DOI 10.1182/blood-2008-07-169417.
HEMATOPOIESIS AND STEM CELLS SCL and associated proteins distinguish active from repressive GATA transcription factor complexes1 Division of Hematology, The Children's Hospital of Philadelphia, PA; 2 Department of Biology, University of Pennsylvania, Philadelphia; 3 Center for Comparative Genomics and Bioinformatics, Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park; and 4 University of Pennsylvania School of Medicine, Philadelphia
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, Ldb1, 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.
This article has been cited by other articles:
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Copyright © 2009 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||