2. Academic Validation
  3. Mitotic bookmarking by SWI/SNF subunits

Mitotic bookmarking by SWI/SNF subunits

  • Nature. 2023 May 24. doi: 10.1038/s41586-023-06085-6.
Zhexin Zhu # 1,  Xiaolong Chen # 2,  Ao Guo 3,  Trishabelle Manzano 4,  Patrick J Walsh 4,  Kendall M Wills 4,  Rebecca Halliburton 4,  Sandi Radko-Juettner 4 5,  Raymond D Carter 4,  Janet F Partridge 4,  Douglas R Green 3,  Jinghui Zhang 2,  Charles W M Roberts 6
Affiliations

Affiliations

  • 1 Division of Molecular Oncology, Department of Oncology, St Jude Children's Research Hospital, Memphis, TN, USA. zhexin.zhu@stjude.org.
  • 2 Department of Computational Biology, St Jude Children's Research Hospital, Memphis, TN, USA.
  • 3 Department of Immunology, St Jude Children's Research Hospital, Memphis, TN, USA.
  • 4 Division of Molecular Oncology, Department of Oncology, St Jude Children's Research Hospital, Memphis, TN, USA.
  • 5 St Jude Graduate School of Biomedical Sciences, St Jude Children's Research Hospital, Memphis, TN, USA.
  • 6 Division of Molecular Oncology, Department of Oncology, St Jude Children's Research Hospital, Memphis, TN, USA. charles.roberts@stjude.org.
  • # Contributed equally.
PMID: 37225980 DOI: 10.1038/s41586-023-06085-6
Abstract

For cells to initiate and sustain a differentiated state, it is necessary that a 'memory' of this state is transmitted through mitosis to the daughter cells1-3. Mammalian switch/sucrose non-fermentable (SWI/SNF) complexes (also known as Brg1/Brg-associated factors, or BAF) control cell identity by modulating chromatin architecture to regulate gene expression4-7, but whether they participate in cell fate memory is unclear. Here we provide evidence that subunits of SWI/SNF act as mitotic bookmarks to safeguard cell identity during cell division. The SWI/SNF core subunits SMARCE1 and SMARCB1 are displaced from enhancers but are bound to promoters during mitosis, and we show that this binding is required for appropriate reactivation of bound genes after mitotic exit. Ablation of SMARCE1 during a single mitosis in mouse embryonic stem cells is sufficient to disrupt gene expression, impair the occupancy of several established bookmarks at a subset of their targets and cause aberrant neural differentiation. Thus, SWI/SNF subunit SMARCE1 has a mitotic bookmarking role and is essential for heritable epigenetic fidelity during transcriptional reprogramming.

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