FLASH is essential during early embryogenesis and cooperates with p73 to regulate histone gene transcription

A. De Cola, L. Bongiorno-Borbone, E. Bianchi, D. Barcaroli, E. Carletti, R. A. Knight, C. Di Ilio, G. Melino, C. Sette, V. De Laurenzi

Research output: Contribution to journalArticlepeer-review

Abstract

Replication-dependent histone gene expression is a fundamental process occurring in S-phase under the control of the cyclin-E/CDK2 complex. This process is regulated by a number of proteins, including Flice-Associated Huge Protein (FLASH) (CASP8AP2), concentrated in specific nuclear organelles known as HLBs. FLASH regulates both histone gene transcription and mRNA maturation, and its downregulation in vitro results in the depletion of the histone pull and cell-cycle arrest in S-phase. Here we show that the transcription factor p73 binds to FLASH and is part of the complex that regulates histone gene transcription. Moreover, we created a novel gene trap to disrupt FLASH in mice, and we show that homozygous deletion of FLASH results in early embryonic lethality, owing to arrest of FLASH -/- embryos at the morula stage. These results indicate that FLASH is an essential, non-redundant regulator of histone transcription and cell cycle during embryogenesis.

Original languageEnglish
Pages (from-to)573-582
Number of pages10
JournalOncogene
Volume31
Issue number5
DOIs
Publication statusPublished - Feb 2 2012

Keywords

  • Cajal bodies
  • FLASH
  • Histone Locus Bodies
  • NPAT

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

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