---
OA_place: publisher
OA_type: hybrid
_id: '18645'
abstract:
- lang: eng
  text: Gene expression during natural and induced reprogramming is controlled by
    pioneer transcription factors that initiate transcription from closed chromatin.
    Nr5a2 is a key pioneer factor that regulates zygotic genome activation in totipotent
    embryos, pluripotency in embryonic stem cells and metabolism in adult tissues,
    but the mechanism of its pioneer activity remains poorly understood. Here, we
    present a cryo-electron microscopy structure of human NR5A2 bound to a nucleosome.
    The structure shows that the conserved carboxy-terminal extension (CTE) loop of
    the NR5A2 DNA-binding domain competes with a DNA minor groove anchor of the nucleosome
    and releases entry-exit site DNA. Mutational analysis showed that NR5A2 D159 of
    the CTE is dispensable for DNA binding but required for stable nucleosome association
    and persistent DNA ‘unwrapping’. These findings suggest that NR5A2 belongs to
    an emerging class of pioneer factors that can use DNA minor groove anchor competition
    to destabilize nucleosomes and facilitate gene expression during reprogramming.
acknowledgement: 'We are very grateful to K. Abe, L. G. Hernandez, C. Kobayashi, K.
  Straßer and M. Zaczek for their contributions and technical support. We thank N.
  Thomä for advice on SeEN-seq. We are grateful to A. Musacchio for insightful discussions.
  We thank J.-M. Peters for critical reading of the manuscript and all members of
  K.T.’s laboratory for discussions. We thank T. Schäfer at the cryo-EM facility for
  assistance in cryo-EM data collection, and R. H. Kim for sequencing at the NGS facility,
  MPIB. K.T. is an Honorary Professor at the Department of Biology, Ludwig-Maximilians-University,
  Munich. Funding: European Research Council grant ERC-CoG-818556 TotipotentZygotChrom
  (K.T.). European Research Council grant ERC-StG-804098 ReplisomeBypass (K.D.). Max
  Planck Society (K.T., K.D.).'
article_processing_charge: Yes (in subscription journal)
article_type: original
author:
- first_name: Wataru
  full_name: Kobayashi, Wataru
  last_name: Kobayashi
- first_name: Anna H.
  full_name: Sappler, Anna H.
  last_name: Sappler
- first_name: Daniel
  full_name: Bollschweiler, Daniel
  last_name: Bollschweiler
- first_name: Maximilian
  full_name: Kümmecke, Maximilian
  last_name: Kümmecke
- first_name: Jérôme
  full_name: Basquin, Jérôme
  last_name: Basquin
- first_name: Eda Nur
  full_name: Arslantas, Eda Nur
  id: 36978b4e-2966-11ef-a72f-b3740ef1cd11
  last_name: Arslantas
- first_name: Siwat
  full_name: Ruangroengkulrith, Siwat
  last_name: Ruangroengkulrith
- first_name: Renate
  full_name: Hornberger, Renate
  last_name: Hornberger
- first_name: Karl
  full_name: Duderstadt, Karl
  last_name: Duderstadt
- first_name: Kikuë
  full_name: Tachibana, Kikuë
  last_name: Tachibana
citation:
  ama: Kobayashi W, Sappler AH, Bollschweiler D, et al. Nucleosome-bound NR5A2 structure
    reveals pioneer factor mechanism by DNA minor groove anchor competition. <i>Nature
    Structural &#38; Molecular Biology</i>. 2024;31:757-766. doi:<a href="https://doi.org/10.1038/s41594-024-01239-0">10.1038/s41594-024-01239-0</a>
  apa: Kobayashi, W., Sappler, A. H., Bollschweiler, D., Kümmecke, M., Basquin, J.,
    Arslantas, E. N., … Tachibana, K. (2024). Nucleosome-bound NR5A2 structure reveals
    pioneer factor mechanism by DNA minor groove anchor competition. <i>Nature Structural
    &#38; Molecular Biology</i>. Springer Nature. <a href="https://doi.org/10.1038/s41594-024-01239-0">https://doi.org/10.1038/s41594-024-01239-0</a>
  chicago: Kobayashi, Wataru, Anna H. Sappler, Daniel Bollschweiler, Maximilian Kümmecke,
    Jérôme Basquin, Eda Nur Arslantas, Siwat Ruangroengkulrith, Renate Hornberger,
    Karl Duderstadt, and Kikuë Tachibana. “Nucleosome-Bound NR5A2 Structure Reveals
    Pioneer Factor Mechanism by DNA Minor Groove Anchor Competition.” <i>Nature Structural
    &#38; Molecular Biology</i>. Springer Nature, 2024. <a href="https://doi.org/10.1038/s41594-024-01239-0">https://doi.org/10.1038/s41594-024-01239-0</a>.
  ieee: W. Kobayashi <i>et al.</i>, “Nucleosome-bound NR5A2 structure reveals pioneer
    factor mechanism by DNA minor groove anchor competition,” <i>Nature Structural
    &#38; Molecular Biology</i>, vol. 31. Springer Nature, pp. 757–766, 2024.
  ista: Kobayashi W, Sappler AH, Bollschweiler D, Kümmecke M, Basquin J, Arslantas
    EN, Ruangroengkulrith S, Hornberger R, Duderstadt K, Tachibana K. 2024. Nucleosome-bound
    NR5A2 structure reveals pioneer factor mechanism by DNA minor groove anchor competition.
    Nature Structural &#38; Molecular Biology. 31, 757–766.
  mla: Kobayashi, Wataru, et al. “Nucleosome-Bound NR5A2 Structure Reveals Pioneer
    Factor Mechanism by DNA Minor Groove Anchor Competition.” <i>Nature Structural
    &#38; Molecular Biology</i>, vol. 31, Springer Nature, 2024, pp. 757–66, doi:<a
    href="https://doi.org/10.1038/s41594-024-01239-0">10.1038/s41594-024-01239-0</a>.
  short: W. Kobayashi, A.H. Sappler, D. Bollschweiler, M. Kümmecke, J. Basquin, E.N.
    Arslantas, S. Ruangroengkulrith, R. Hornberger, K. Duderstadt, K. Tachibana, Nature
    Structural &#38; Molecular Biology 31 (2024) 757–766.
date_created: 2024-12-11T09:10:54Z
date_published: 2024-05-01T00:00:00Z
date_updated: 2024-12-11T10:56:35Z
day: '01'
doi: 10.1038/s41594-024-01239-0
extern: '1'
intvolume: '        31'
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://doi.org/10.1038/s41594-024-01239-0
month: '05'
oa: 1
oa_version: Published Version
page: 757-766
publication: Nature Structural & Molecular Biology
publication_identifier:
  eissn:
  - 1545-9985
  issn:
  - 1545-9993
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: Nucleosome-bound NR5A2 structure reveals pioneer factor mechanism by DNA minor
  groove anchor competition
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 31
year: '2024'
...