The high mobility group protein HMG1 can reversibly inhibit class II gene transcription by interaction with the TATA-binding protein.
Regulation of transcription by RNA polymerase II in eukaryotic cells requires both basal and accessory factors, which interact through specific protein-DNA or protein-protein interactions. The high mobility group 1 protein (HMG1) was previously demonstrated to be a nonhistone chromatin-associated protein, which selectively recognizes cruciform DNA rather than a specific primary sequence element. During our investigations of proteins that interact with TFIID, we found that purified mammalian HMG1, as well as recombinant human HMG1, can interact with TATA-binding protein (TBP) in the presence of a TATA box-containing oligonucleotide to form a specific HMG1.TBP.promoter complex. This complex prevents TFIIB binding to TBP and consequently blocks formation of the preinitiation complex. In contrast, TFIIA can compete with HMG1 for binding to TBP. In an in vitro transcription assay reconstituted with highly purified or recombinant general factors, HMG1 is able to inhibit transcription by RNA polymerase II over 30-fold. As expected, addition of TFIIA can partially reverse this repression in a concentration-dependent manner. These results demonstrate that HMG1, a chromatin-associated protein, has the potential to act as a TBP-dependent negative transcription factor and may provide an important link between chromatin structure and the modulation of class II gene transcription.
Ge
H
H
Laboratory of Biochemistry and Molecular Biology, Rockefeller University, New York, New York 10021.
Roeder
R G
RG
D000818:Animals; D001483:Base Sequence; D002417:Cattle; D004268:DNA-Binding Proteins / Q000378:metabolism* / Q000494:pharmacology; D005786:Gene Expression Regulation; D006609:High Mobility Group Proteins / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes / Q000737:chemistry; D011485:Protein Binding; D012319:RNA Polymerase II / Q000378:metabolism*; D011994:Recombinant Proteins; D035181:TATA-Box Binding Protein; D035561:Transcription Factor TFIIA; D035581:Transcription Factor TFIIB; D014157:Transcription Factors / Q000378:metabolism* / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects
D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D046911:Macromolecular Substances; D015345:Oligonucleotide Probes; D011994:Recombinant Proteins; D035181:TATA-Box Binding Protein; D035561:Transcription Factor TFIIA; D035581:Transcription Factor TFIIB; D014157:Transcription Factors; D012319:RNA Polymerase II