Concerted epigenetic signatures inheritance at PcG targets through replication

Chiara Lanzuolo*, Federica Lo Sardo, Valerio Orlando

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Polycomb group of proteins (PcG), by controlling gene silencing transcriptional programs through cell cycle, lock cell identity and memory. Recent chromatin genome-wide studies indicate that PcG targets sites are bivalent domains with overlapping repressive H3K27me3 and active H3K4me3 mark domains. During S phase, the stability of epigenetic signatures is challenged by the replication fork passage. Hence, specific mechanisms of epigenetic inheritance might be provided to preserve epigenome structures. Recently, we have identified a critical time window before replication, during which high levels of PcG binding and histone marks on BX-C PRE target sites set the stage for subsequent dilution of epigenomic components, allowing proper transmission of epigenetic signatures to the next generation. Here, we extended this analysis to promoter elements, showing the same mechanism of inheritance. Furthermore, to gain insight into the inheritance of PREs bivalent marks, we analyzed dynamics of H3K4me3 deposition, a mark that correlates with transcriptionally active chromatin. Likewise, we found an early S-phase enrichment of H3K4me3 mark preceding the replication- dependent dilution. This evidence suggests that all epigenetic marks are inherited simultaneously to ensure their correct propagation through replication and to protect the "bivalency" of PREs.

Original languageEnglish (US)
Pages (from-to)1296-1300
Number of pages5
JournalCell Cycle
Volume11
Issue number7
DOIs
StatePublished - Apr 1 2012
Externally publishedYes

Bibliographical note

Funding Information:
We thank J. Muller and R. Paro for kindly providing antibodies that have been essential for this study. We are grateful to Gennaro Oliva for help in graphic design. We thank Maria Vivo, Beatrice Bodega and all members of the lab for stimulating discussions and constructive criticisms. This work was supported by Telethon (grant S00094TELA) and Associazione Italiana Ricerca sul Cancro (AIRC) to V.O.

Keywords

  • Bivalent domain
  • Chromatin
  • DNA replication
  • Epigenetic inheritance
  • Histone marks
  • PRE
  • Polycomb
  • S phase

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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