Regulation of transcription of the steroidogenic acute regulatory protein (StAR) gene: temporal and spatial changes in transcription factor binding and histone modification.
We examined the binding of transcription factors and histone modifications associated with induction of expression of the steroidogenic acute regulatory protein (StAR) gene in MA-10 cells using a quantitative chromatin immunoprecipitation (ChIP) assay. GATA-4, SF-1/Ad4BP, and cyclic AMP response element binding protein binding protein (CBP) bind rapidly to the StAR proximal promoter, but in different patterns following 8-Br-cAMP stimulation. Concomitantly, histone modifications occur in a spatial and temporal sequence including increased association of acetylated histone H3 with the proximal promoter region, increased association of dimethylated lysine 4 histone H3 with exonic sequences, a modification that marks actively transcribed regions, and reduced association of a marker linked to gene silencing (lysine 9 dimethylated histone H3). Our findings demonstrate that transcription factors and coactivators are rapidly associated with the StAR proximal promoter, that the patterns of binding differ which has implications for postulated direct interactions among these factors, and that multiple histone modifications are demonstrable in a spatially- and temporally-specific pattern along the StAR gene. These observations suggest that a combinatorial code of transcription factors including reciprocal changes in histone modifications associated with active transcription and gene silencing control StAR gene expression.
Hiroi
Hisahiko
H
Center for Research on Reproduction and Women's Health, University of Pennsylvania Medical Center, 1354 BRB, 421 Curie Boulevard, Philadelphia, PA 19104, USA.
Christenson
Lane K
LK
Strauss
Jerome F
JF
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000107:Acetylation; D000818:Animals; D002843:Chromatin / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006657:Histones / Q000378:metabolism*; D007984:Leydig Cell Tumor; D008745:Methylation; D051379:Mice; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D000098682:Steroidogenic Acute Regulatory Protein
D002843:Chromatin; D006657:Histones; D010750:Phosphoproteins; D012333:RNA, Messenger; D014157:Transcription Factors; D000098682:Steroidogenic Acute Regulatory Protein; D015124:8-Bromo Cyclic Adenosine Monophosphate