Antagonistic regulation of beta-globin gene expression by helix-loop-helix proteins USF and TFII-I.
The human beta-globin genes are expressed in a developmental stage-specific manner in erythroid cells. Gene-proximal cis-regulatory DNA elements and interacting proteins restrict the expression of the genes to the embryonic, fetal, or adult stage of erythropoiesis. In addition, the relative order of the genes with respect to the locus control region contributes to the temporal regulation of the genes. We have previously shown that transcription factors TFII-I and USF interact with the beta-globin promoter in erythroid cells. Herein we demonstrate that reducing the activity of USF decreased beta-globin gene expression, while diminishing TFII-I activity increased beta-globin gene expression in erythroid cell lines. Furthermore, a reduction of USF activity resulted in a significant decrease in acetylated H3, RNA polymerase II, and cofactor recruitment to the locus control region and to the adult beta-globin gene. The data suggest that TFII-I and USF regulate chromatin structure accessibility and recruitment of transcription complexes in the beta-globin gene locus and play important roles in restricting beta-globin gene expression to the adult stage of erythropoiesis.
Crusselle-Davis
Valerie J
VJ
Department of Biochemistry and Molecular Biology, College of Medicine, University of Florida, P.O. Box 100245, 1600 SW Archer Road, Gainesville, FL 32610, USA.
Vieira
Karen F
KF
Zhou
Zhuo
Z
Anantharaman
Archana
A
Bungert
Jörg
J
D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000166:cytology; D041905:Erythroid Cells / Q000166:cytology; D018507:Gene Expression Regulation, Developmental; D005914:Globins / Q000235:genetics*; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D020014:K562 Cells; D051379:Mice; D008957:Models, Genetic; D011485:Protein Binding; D012319:RNA Polymerase II / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology; D019473:Transcription Factors, TFII / Q000378:metabolism*; D014158:Transcription, Genetic; D051720:Upstream Stimulatory Factors / Q000378:metabolism*; D050880:p300-CBP Transcription Factors / Q000378:metabolism; D000099186:Histone Deacetylase 3
D005914:Globins; D006655:Histone Deacetylases; D012319:RNA Polymerase II; D012097:Repressor Proteins; D019473:Transcription Factors, TFII; D051720:Upstream Stimulatory Factors; D050880:p300-CBP Transcription Factors; D000099186:Histone Deacetylase 3; C104259:GTF2I protein, human