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PR-Set7 and H4K20me1: at the crossroads of genome integrity, cell cycle, chromosome condensation, and transcription

Journal

GENES & DEVELOPMENT
Volume 26, Issue 4, Pages 325-337

Publisher

COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.177444.111

Keywords

PR-Set7; H4K20me1; chromatin; cell cycle; DNA damage

Funding

  1. National Institutes of Health [GM64844, GM037120]
  2. Howard Hughes Medical Institute
  3. Ministry of Education, Science, Sports, and Culture [23616009]
  4. Grants-in-Aid for Scientific Research [23616009] Funding Source: KAKEN

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Histone post-translational modifications impact many aspects of chromatin and nuclear function. Histone H4 Lys 20 methylation (H4K20me) has been implicated in regulating diverse processes ranging from the DNA damage response, mitotic condensation, and DNA replication to gene regulation. PR-Set7/Set8/KMT5a is the sole enzyme that catalyzes monomethylation of H4K20 (H4K20me1). It is required for maintenance of all levels of H4K20me, and, importantly, loss of PR-Set7 is catastrophic for the earliest stages of mouse embryonic development. These findings have placed PR-Set7, H4K20me, and proteins that recognize this modification as central nodes of many important pathways. In this review, we discuss the mechanisms required for regulation of PR-Set7 and H4K20me1 levels and attempt to unravel the many functions attributed to these proteins.

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