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Interrogating Histone Acetylation and BRD4 as Mitotic Bookmarks of Transcription.

Cell reports | 2019

Global changes in chromatin organization and the cessation of transcription during mitosis are thought to challenge the resumption of appropriate transcription patterns after mitosis. The acetyl-lysine binding protein BRD4 has been previously suggested to function as a transcriptional "bookmark" on mitotic chromatin. Here, genome-wide location analysis of BRD4 in erythroid cells, combined with data normalization and peak characterization approaches, reveals that BRD4 widely occupies mitotic chromatin. However, removal of BRD4 from mitotic chromatin does not impair post-mitotic activation of transcription. Additionally, histone mass spectrometry reveals global preservation of most posttranslational modifications (PTMs) during mitosis. In particular, H3K14ac, H3K27ac, H3K122ac, and H4K16ac widely mark mitotic chromatin, especially at lineage-specific genes, and predict BRD4 mitotic binding genome wide. Therefore, BRD4 is likely not a mitotic bookmark but only a "passenger." Instead, mitotic histone acetylation patterns may constitute the actual bookmarks that restore lineage-specific transcription patterns after mitosis.

Pubmed ID: 30970245 RIS Download

Associated grants

  • Agency: NIDDK NIH HHS, United States
    Id: F30 DK108469
  • Agency: NIDDK NIH HHS, United States
    Id: T32 DK007780
  • Agency: NHLBI NIH HHS, United States
    Id: T32 HL007439
  • Agency: NIDDK NIH HHS, United States
    Id: R01 DK058044
  • Agency: NCI NIH HHS, United States
    Id: P01 CA196539
  • Agency: NIDDK NIH HHS, United States
    Id: R37 DK058044
  • Agency: NIDDK NIH HHS, United States
    Id: R24 DK106766
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI118891
  • Agency: NIDDK NIH HHS, United States
    Id: R01 DK054937
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM110174

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