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.

De Cola, A., BONGIORNO BORBONE, L., Bianchi, E., Barcaroli, D., Carletti, E., Knight, R., et al. (2012). FLASH is essential during early embryogenesis and cooperates with p73 to regulate histone gene transcription. ONCOGENE, 31(5), 573-582 [10.1038/onc.2011.274].

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

BONGIORNO BORBONE, LUCILLA;MELINO, GENNARO;SETTE, CLAUDIO;
2012-02-02

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.
2-feb-2012
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/11 - BIOLOGIA MOLECOLARE
English
Embryonic Development; Animals; Histones; HEK293 Cells; Humans; Transcription, Genetic; Mice, Knockout; Calcium-Binding Proteins; Nuclear Proteins; RNA Interference; Genes, Lethal; Embryo, Mammalian; Cell Cycle; Male; DNA-Binding Proteins; Apoptosis Regulatory Proteins; Cell Line, Tumor; Mice; HCT116 Cells; Reverse Transcriptase Polymerase Chain Reaction; Protein Binding; Tumor Suppressor Proteins; Mice, 129 Strain; Blotting, Western; Mice, Inbred C57BL; Gene Expression Regulation, Developmental; Female
De Cola, A., BONGIORNO BORBONE, L., Bianchi, E., Barcaroli, D., Carletti, E., Knight, R., et al. (2012). FLASH is essential during early embryogenesis and cooperates with p73 to regulate histone gene transcription. ONCOGENE, 31(5), 573-582 [10.1038/onc.2011.274].
De Cola, A; BONGIORNO BORBONE, L; Bianchi, E; Barcaroli, D; Carletti, E; Knight, R; Di, I; Melino, G; Sette, C; C, ; De Laurenzi, V
Articolo su rivista
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/78444
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 25
  • ???jsp.display-item.citation.isi??? 23
social impact