Title: High-resolution and high-accuracy topographic and transcriptional maps of the nucleosome barrier

Abstract

Nucleosomes represent mechanical and energetic barriers that RNA Polymerase II (Pol II) must overcome during transcription. A high-resolution description of the barrier topography, its modulation by epigenetic modifications, and their effects on Pol II nucleosome crossing dynamics, is still missing. Here, we obtain topographic and transcriptional (Pol II residence time) maps of canonical, H2A.Z, and monoubiquitinated H2B (uH2B) nucleosomes at near base-pair resolution and accuracy. Pol II crossing dynamics are complex, displaying pauses at specific loci, backtracking, and nucleosome hopping between wrapped states. While H2A.Z widens the barrier, uH2B heightens it, and both modifications greatly lengthen Pol II crossing time. Using the dwell times of Pol II at each nucleosomal position we extract the energetics of the barrier. The orthogonal barrier modifications of H2A.Z and uH2B, and their effects on Pol II dynamics rationalize their observed enrichment in +1 nucleosomes and suggest a mechanism for selective control of gene expression.

Authors:

Chen, Zhijie  ^[1];

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• Search DOE PAGES for ORCID "0000-0003-1376-5750"

Gabizon, Ronen  ^[2];

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• Search DOE PAGES for ORCID "0000-0002-3626-5073"

Brown, Aidan I.  ^[3];

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• Search DOE PAGES for ORCID "0000-0002-6600-8289"

Lee, Antony  ^[4];

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• Search DOE PAGES for ORCID "0000-0003-2193-5369"

Song, Aixin  ^[5];

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• Search DOE PAGES for ORCID "0000-0002-4377-7528"

Díaz-Celis, César  ^[1];

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• Search DOE PAGES for ORCID "0000-0002-6659-8434"

Kaplan, Craig D.  ^[6];

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• Search DOE PAGES for ORCID "0000-0002-7518-695X"

Koslover, Elena F.  ^[3];

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• Search DOE PAGES for ORCID "0000-0003-4139-9209"

Yao, Tingting  ^[5];

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• Search DOE PAGES for ORCID "0000-0003-4101-9691"

Bustamante, Carlos  ^[7]

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• Search DOE PAGES for ORCID "0000-0002-2970-0073"

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+ Show Author Affiliations

1. Institute for Quantitative Biosciences-QB3, University of California, Berkeley, Berkeley, United States, Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, United States
2. Institute for Quantitative Biosciences-QB3, University of California, Berkeley, Berkeley, United States
3. Department of Physics, University of California, San Diego, San Diego, United States
4. Department of Physics, University of California, Berkeley, Berkeley, United States
5. Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, United States
6. Department of Biological Sciences, University of Pittsburgh, Pittsburgh, United States
7. Institute for Quantitative Biosciences-QB3, University of California, Berkeley, Berkeley, United States, Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, United States, Department of Physics, University of California, Berkeley, Berkeley, United States, Jason L Choy Laboratory of Single-Molecule Biophysics, University of California, Berkeley, Berkeley, United States, Biophysics Graduate Group, University of California, Berkeley, Berkeley, United States

Publication Date:

Wed Jul 31 00:00:00 EDT 2019

Research Org.:

Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Org.:

USDOE Office of Science (SC), Basic Energy Sciences (BES)

OSTI Identifier:

1545911

Alternate Identifier(s):

OSTI ID: 1545912; OSTI ID: 1628910

Grant/Contract Number:  

Nanomachine Program under Contract DE-AC02-05CH11231; AC02-05CH11231; R01GM032543; R01GM071552; R01GM098401; R01GM097260; FG-2018–10394

Resource Type:

Published Article

Journal Name:

eLife

Additional Journal Information:

Journal Name: eLife Journal Volume: 8; Journal ID: ISSN 2050-084X

Publisher:

eLife Sciences Publications, Ltd.

Country of Publication:

United States

Language:

English

Subject:

59 BASIC BIOLOGICAL SCIENCES; Life Sciences & Biomedicine - Other Topics