SCL and associated proteins distinguish active from repressive GATA transcription factor complexes.
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.
Tripic
Tamara
T
Division of Hematology, The Children's Hospital of Philadelphia, PA 19104, USA.
Deng
Wulan
W
Cheng
Yong
Y
Zhang
Ying
Y
Vakoc
Christopher R
CR
Gregory
Gregory D
GD
Hardison
Ross C
RC
Blobel
Gerd A
GA
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics* / Q000378:metabolism; D001773:Blood Cells / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D050982:GATA1 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D047468:Immunoprecipitation; D060588:LIM Domain Proteins; D008667:Metalloproteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014158:Transcription, Genetic
D048868:Adaptor Proteins, Signal Transducing; D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D050982:GATA1 Transcription Factor; D060588:LIM Domain Proteins; D008667:Metalloproteins; D011518:Proto-Oncogene Proteins; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; C494689:Gata1 protein, mouse; C513188:Lmo2 protein, mouse; C489366:Tal1 protein, mouse