1. Interrogating Histone Acetylation and BRD4 as Mitotic Bookmarks of Transcription.
- Author
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Behera V, Stonestrom AJ, Hamagami N, Hsiung CC, Keller CA, Giardine B, Sidoli S, Yuan ZF, Bhanu NV, Werner MT, Wang H, Garcia BA, Hardison RC, and Blobel GA
- Subjects
- Acetylation, Animals, Chromatin genetics, Chromatin metabolism, Histones genetics, Mice, Mitosis physiology, Nuclear Proteins genetics, Transcription Factors genetics, Transcription, Genetic, Histones metabolism, Nuclear Proteins metabolism, Transcription Factors metabolism
- Abstract
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., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2019
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