Structural analysis of nucleosomal barrier to transcription

Daria A. Gaykalova; Olga I. Kulaeva; Olesya Volokh; Alexey K. Shaytan; Fu Kai Hsieh; Mikhail P. Kirpichnikov; Olga S. Sokolova; Vasily M. Studitsky

doi:10.1073/pnas.1508371112

Structural analysis of nucleosomal barrier to transcription

Daria A. Gaykalova, Olga I. Kulaeva, Olesya Volokh, Alexey K. Shaytan, Fu Kai Hsieh, Mikhail P. Kirpichnikov, Olga S. Sokolova, Vasily M. Studitsky

School of Medicine

Research output: Contribution to journal › Article › peer-review

32 Scopus citations

Abstract

Thousands of human and Drosophila genes are regulated at the level of transcript elongation and nucleosomes are likely targets for this regulation. However, the molecular mechanisms of formation of the nucleosomal barrier to transcribing RNA polymerase II (Pol II) and nucleosome survival during/after transcription remain unknown. Here we show that both DNA-histone interactions and Pol II backtracking contribute to formation of the barrier and that nucleosome survival during transcription likely occurs through allosterically stabilized histone-histone interactions. Structural analysis indicates that after Pol II encounters the barrier, the enzyme backtracks and nucleosomal DNA recoils on the octamer, locking Pol II in the arrested state. DNA is displaced from one of the H2A/H2B dimers that remains associatedwith the octamer. The data reveal the importance of intranucleosomal DNA-protein and protein-protein interactions during conformational changes in the nucleosome structure on transcription. Mechanisms of nucleosomal barrier formation and nucleosome survival during transcription are proposed.

Original language	English (US)
Pages (from-to)	E5787-E5795
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	112
Issue number	43
DOIs	https://doi.org/10.1073/pnas.1508371112
State	Published - Oct 27 2015

Keywords

Backtracking
Chromatin
Elongation
RNA polymerase II
Transcription

ASJC Scopus subject areas

General

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10.1073/pnas.1508371112

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title = "Structural analysis of nucleosomal barrier to transcription",

abstract = "Thousands of human and Drosophila genes are regulated at the level of transcript elongation and nucleosomes are likely targets for this regulation. However, the molecular mechanisms of formation of the nucleosomal barrier to transcribing RNA polymerase II (Pol II) and nucleosome survival during/after transcription remain unknown. Here we show that both DNA-histone interactions and Pol II backtracking contribute to formation of the barrier and that nucleosome survival during transcription likely occurs through allosterically stabilized histone-histone interactions. Structural analysis indicates that after Pol II encounters the barrier, the enzyme backtracks and nucleosomal DNA recoils on the octamer, locking Pol II in the arrested state. DNA is displaced from one of the H2A/H2B dimers that remains associatedwith the octamer. The data reveal the importance of intranucleosomal DNA-protein and protein-protein interactions during conformational changes in the nucleosome structure on transcription. Mechanisms of nucleosomal barrier formation and nucleosome survival during transcription are proposed.",

keywords = "Backtracking, Chromatin, Elongation, RNA polymerase II, Transcription",

author = "Gaykalova, {Daria A.} and Kulaeva, {Olga I.} and Olesya Volokh and Shaytan, {Alexey K.} and Hsieh, {Fu Kai} and Kirpichnikov, {Mikhail P.} and Sokolova, {Olga S.} and Studitsky, {Vasily M.}",

note = "Publisher Copyright: {\textcopyright} 2015 PNAS.",

year = "2015",

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doi = "10.1073/pnas.1508371112",

language = "English (US)",

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T1 - Structural analysis of nucleosomal barrier to transcription

AU - Gaykalova, Daria A.

AU - Kulaeva, Olga I.

AU - Volokh, Olesya

AU - Shaytan, Alexey K.

AU - Hsieh, Fu Kai

AU - Kirpichnikov, Mikhail P.

AU - Sokolova, Olga S.

AU - Studitsky, Vasily M.

PY - 2015/10/27

Y1 - 2015/10/27

N2 - Thousands of human and Drosophila genes are regulated at the level of transcript elongation and nucleosomes are likely targets for this regulation. However, the molecular mechanisms of formation of the nucleosomal barrier to transcribing RNA polymerase II (Pol II) and nucleosome survival during/after transcription remain unknown. Here we show that both DNA-histone interactions and Pol II backtracking contribute to formation of the barrier and that nucleosome survival during transcription likely occurs through allosterically stabilized histone-histone interactions. Structural analysis indicates that after Pol II encounters the barrier, the enzyme backtracks and nucleosomal DNA recoils on the octamer, locking Pol II in the arrested state. DNA is displaced from one of the H2A/H2B dimers that remains associatedwith the octamer. The data reveal the importance of intranucleosomal DNA-protein and protein-protein interactions during conformational changes in the nucleosome structure on transcription. Mechanisms of nucleosomal barrier formation and nucleosome survival during transcription are proposed.

AB - Thousands of human and Drosophila genes are regulated at the level of transcript elongation and nucleosomes are likely targets for this regulation. However, the molecular mechanisms of formation of the nucleosomal barrier to transcribing RNA polymerase II (Pol II) and nucleosome survival during/after transcription remain unknown. Here we show that both DNA-histone interactions and Pol II backtracking contribute to formation of the barrier and that nucleosome survival during transcription likely occurs through allosterically stabilized histone-histone interactions. Structural analysis indicates that after Pol II encounters the barrier, the enzyme backtracks and nucleosomal DNA recoils on the octamer, locking Pol II in the arrested state. DNA is displaced from one of the H2A/H2B dimers that remains associatedwith the octamer. The data reveal the importance of intranucleosomal DNA-protein and protein-protein interactions during conformational changes in the nucleosome structure on transcription. Mechanisms of nucleosomal barrier formation and nucleosome survival during transcription are proposed.

KW - Backtracking

KW - Chromatin

KW - Elongation

KW - RNA polymerase II

KW - Transcription

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Structural analysis of nucleosomal barrier to transcription

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