Recruitment of coregulator complexes to the beta-globin gene locus by TFII-I and upstream stimulatory factor.
Upstream stimulatory factor and TFII-I are ubiquitously expressed helix-loop-helix transcription factors that interact with E-box sequences and or initiator elements. We previously demonstrated that upstream stimulatory factor is an activator of beta-globin gene expression whereas TFII-I is a repressor. In the present study, we demonstrate that upstream stimulatory factor interacts with the coactivator p300 and that this interaction is restricted to erythroid cells expressing the adult beta-globin gene. Furthermore, we demonstrate that Suz12, a component of the polycomb repressor complex 2, is recruited to the beta-globin gene. Reducing expression of Suz12 significantly activates beta-globin gene expression in an erythroid cell line with an embryonic phenotype. Suz12 also interacts with the adult beta-globin gene during early stages of erythroid differentiation of mouse embryonic stem cells. Our data suggest that TFII-I contributes to the recruitment of the polycomb repressor complex 2 complex to the beta-globin gene. Together, these data demonstrate that the antagonistic activities of upstream stimulatory factor and TFII-I on beta-globin gene expression are mediated at least in part by protein complexes that render the promoter associated chromatin accessible or inaccessible for the transcription complex.
Crusselle-Davis
Valerie J
VJ
Department of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, FL 32610, USA.
Zhou
Zhuo
Z
Anantharaman
Archana
A
Moghimi
Babak
B
Dodev
Tihomir
T
Huang
Suming
S
Bungert
Jörg
J
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation; D041905:Erythroid Cells / Q000166:cytology; D018507:Gene Expression Regulation, Developmental; D005914:Globins / Q000235:genetics / Q000378:metabolism*; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D020014:K562 Cells; D051379:Mice; D009363:Neoplasm Proteins; D009687:Nuclear Proteins / Q000378:metabolism; D063151:Polycomb Repressive Complex 2; D063146:Polycomb-Group Proteins; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology; D014157:Transcription Factors; D019473:Transcription Factors, TFII / Q000378:metabolism*; D051720:Upstream Stimulatory Factors / Q000378:metabolism*; D050880:p300-CBP Transcription Factors / Q000378:metabolism; D000099186:Histone Deacetylase 3
D002352:Carrier Proteins; D005914:Globins; D006655:Histone Deacetylases; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D063151:Polycomb Repressive Complex 2; D063146:Polycomb-Group Proteins; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D014157:Transcription Factors; D019473:Transcription Factors, TFII; D051720:Upstream Stimulatory Factors; D050880:p300-CBP Transcription Factors; D000099186:Histone Deacetylase 3; C430461:SUZ12 protein, human; C494163:Suz12 protein, mouse