2. Academic Validation
  3. BRD2 compartmentalizes the accessible genome

BRD2 compartmentalizes the accessible genome

  • Nat Genet. 2022 Apr;54(4):481-491. doi: 10.1038/s41588-022-01044-9.
Liangqi Xie  # 1 2,  Peng Dong  # 1,  Yifeng Qi 3,  Tsung-Han S Hsieh 2 4,  Brian P English 1,  SeolKyoung Jung 5,  Xingqi Chen 6,  Margherita De Marzio 3,  Rafael Casellas 5,  Howard Y Chang 7,  Bin Zhang 8,  Robert Tjian 9 10,  Zhe Liu 11
Affiliations

Affiliations

  • 1 Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA.
  • 2 Department of Molecular and Cell Biology, Li Ka Shing Center for Biomedical and Health Sciences, CIRM Center of Excellence, University of California, Berkeley, CA, USA.
  • 3 Departments of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • 4 Howard Hughes Medical Institute, Berkeley, CA, USA.
  • 5 Lymphocyte Nuclear Biology, NIAMS and Center of Cancer Research, NCI, NIH, Bethesda, MD, USA.
  • 6 Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
  • 7 Center for Personal Dynamic Regulomes and Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA.
  • 8 Departments of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA. binz@mit.edu.
  • 9 Department of Molecular and Cell Biology, Li Ka Shing Center for Biomedical and Health Sciences, CIRM Center of Excellence, University of California, Berkeley, CA, USA. jmlim@berkeley.edu.
  • 10 Howard Hughes Medical Institute, Berkeley, CA, USA. jmlim@berkeley.edu.
  • 11 Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA. liuz11@janelia.hhmi.org.
  • # Contributed equally.
PMID: 35410381 DOI: 10.1038/s41588-022-01044-9
Abstract

Mammalian chromosomes are organized into megabase-sized compartments that are further subdivided into topologically associating domains (TADs). While the formation of TADs is dependent on cohesin, the mechanism behind compartmentalization remains enigmatic. Here, we show that the bromodomain and extraterminal (BET) family scaffold protein BRD2 promotes spatial mixing and compartmentalization of active chromatin after cohesin loss. This activity is independent of transcription but requires BRD2 to recognize acetylated targets through its double bromodomain and interact with binding partners with its low-complexity domain. Notably, genome compartmentalization mediated by BRD2 is antagonized on the one hand by cohesin and on the other hand by the BET homolog protein BRD4, both of which inhibit BRD2 binding to chromatin. Polymer simulation of our data supports a BRD2-cohesin interplay model of nuclear topology, in which genome compartmentalization results from a competition between loop extrusion and chromatin-state-specific affinity interactions.

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