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Nat Struct Mol Biol. 2018 Sep;25(9):859-867. doi: 10.1038/s41594-018-0118-5. Epub 2018 Sep 6.

Architecture of Pol II(G) and molecular mechanism of transcription regulation by Gdown1.

Author information

1
Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, New York, NY, USA.
2
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, San Diego, CA, USA.
3
Pfizer Inc., Groton, CT, USA.
4
Laboratory of Mass Spectrometry and Gaseous Ion Chemistry, The Rockefeller University, New York, NY, USA.
5
Department of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
6
Department of Bioengineering and Therapeutic Sciences, Department of Pharmaceutical Chemistry, California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA, USA.
7
Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan.
8
Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, CO, USA.
9
Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, New York, NY, USA. roeder@mail.rockefeller.edu.

Abstract

Tight binding of Gdown1 represses RNA polymerase II (Pol II) function in a manner that is reversed by Mediator, but the structural basis of these processes is unclear. Although Gdown1 is intrinsically disordered, its Pol II interacting domains were localized and shown to occlude transcription factor IIF (TFIIF) and transcription factor IIB (TFIIB) binding by perfect positioning on their Pol II interaction sites. Robust binding of Gdown1 to Pol II is established by cooperative interactions of a strong Pol II binding region and two weaker binding modulatory regions, thus providing a mechanism both for tight Pol II binding and transcription inhibition and for its reversal. In support of a physiological function for Gdown1 in transcription repression, Gdown1 co-localizes with Pol II in transcriptionally silent nuclei of early Drosophila embryos but re-localizes to the cytoplasm during zygotic genome activation. Our study reveals a self-inactivation through Gdown1 binding as a unique mode of repression in Pol II function.

PMID:
30190596
DOI:
10.1038/s41594-018-0118-5

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