Histone H1 represses estrogen receptor alpha transcriptional activity by selectively inhibiting receptor-mediated transcription initiation.
Chromatin is the physiological template for many nuclear processes in eukaryotes, including transcription by RNA polymerase II. In vivo, chromatin is assembled from genomic DNA, core histones, linker histones such as histone H1, and nonhistone chromatin-associated proteins. Histone H1 is thought to act as a general repressor of transcription by promoting the compaction of chromatin into higher-order structures. We have used a biochemical approach, including an in vitro chromatin assembly and transcription system, to examine the effects of histone H1 on estrogen receptor alpha (ER alpha)-mediated transcription with chromatin templates. We show that histone H1 acts as a potent repressor of ligand- and coactivator-regulated transcription by ER alpha. Histone H1 exerts its repressive effect without inhibiting the sequence-specific binding of ER alpha to chromatin or the overall extent of targeted acetylation of nucleosomal histones by the coactivator p300. Instead, histone H1 acts by blocking a specific step in the ER alpha-dependent transcription process, namely, transcription initiation, without affecting transcription reinitiation. Together, our data indicate that histone H1 acts selectively to reduce the overall level of productive transcription initiation by restricting promoter accessibility and preventing the ER alpha-dependent formation of a stable transcription pre-initiation complex.
Cheung
Edwin
E
Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853, USA.
Zarifyan
Alla S
AS
Kraus
W Lee
WL
D000107:Acetylation; D000818:Animals; D002417:Cattle; D002843:Chromatin / Q000378:metabolism; D004257:DNA Polymerase II / Q000378:metabolism; D004330:Drosophila; D047628:Estrogen Receptor alpha; D006657:Histones / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D009687:Nuclear Proteins / Q000378:metabolism; D009707:Nucleosomes / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011960:Receptors, Estrogen / Q000235:genetics* / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism / Q000494:pharmacology; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014981:Xenopus
D002843:Chromatin; D047628:Estrogen Receptor alpha; D006657:Histones; D009687:Nuclear Proteins; D009707:Nucleosomes; D011960:Receptors, Estrogen; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D004257:DNA Polymerase II