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Maintaining Transcriptional Specificity Through Mitosis.

Kenji Ito1, Kenneth S Zaret1

  • 1Institute for Regenerative Medicine and Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA;

Annual Review of Genomics and Human Genetics
|April 20, 2022
PubMed
Summary

Cellular identity is maintained through mitosis via gene expression memory. Recent research highlights low-level promoter transcription and chromosome dynamics, not just transcription factor bookmarking, in ensuring faithful gene reactivation after cell division.

Keywords:
bookmarkingchromosomemitosistranscriptiontranscription factor

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Area of Science:

  • Molecular Biology
  • Cell Biology
  • Epigenetics

Background:

  • All cell types share identical DNA but display unique gene expression patterns.
  • Mitosis involves chromosome condensation and reduced transcription, yet cells precisely re-establish cell-specific gene expression post-mitosis.
  • Previous focus was on transcription factors selectively retained (bookmarking) on chromatin during mitosis.

Purpose of the Study:

  • To review recent findings on the mechanisms ensuring faithful gene expression through mitosis.
  • To explore the role of low-level transcription and chromatin dynamics in mitotic memory.
  • To integrate new insights into histone modifications, cell cycle signaling, and nuclear envelope proteins.

Main Methods:

  • Review of recent scientific literature and studies.
  • Analysis of research on transcription factor retention and chromatin binding during mitosis.
  • Examination of data on promoter activity versus enhancer activity in mitotic memory.

Main Results:

  • Many transcription factors can be retained on mitotic chromatin through nonspecific binding, challenging the bookmarking model.
  • Low-level transcription, particularly via promoters, is increasingly recognized as a key contributor to mitotic memory.
  • New insights reveal the collective roles of chromosome structure dynamics, histone modifications, cell cycle signaling, and nuclear envelope proteins.

Conclusions:

  • Mitotic memory relies on a complex interplay of factors beyond simple transcription factor bookmarking.
  • Promoter-driven transcription and dynamic chromosome regulation are crucial for maintaining cell-specific gene expression fidelity through mitosis.
  • Understanding these mechanisms provides a comprehensive view of how cellular identity is preserved across cell divisions.