FLASH is required for histone transcription and S-phase progression.
Cajal bodies are nuclear subdomains that are involved in maturation of small ribonucleoproteins and frequently associate with small nuclear RNA and histone gene clusters in interphase cells. We have recently identified FADD-like IL-1beta-converting enzyme (FLICE) associated huge protein (FLASH) as an essential component of Cajal bodies. Here we show that FLASH associates with nuclear protein, ataxia-telangiectasia, a component of the cell-cycle-dependent histone gene transcription machinery. Reduction of FLASH expression by RNA interference results in disruption of the normal Cajal body architecture and relocalization of nuclear protein, ataxia-telangiectasia. Furthermore, FLASH down-regulation results in a clear reduction of histone transcription and a dramatic S-phase arrest of the cell cycle. Chromatin immunoprecipitation reveals that FLASH interacts with histone gene promoter sequences. These results identify FLASH as an important component of the machinery required for histone precursor mRNA expression and cell-cycle progression.
Barcaroli
D
D
Medical Research Council, Toxicology Unit, Leicester University, Hodgkin Building, Lancaster Road, Leicester LE1 9HN, United Kingdom.
Bongiorno-Borbone
L
L
Terrinoni
A
A
Hofmann
T G
TG
Rossi
M
M
Knight
R A
RA
Matera
A G
AG
Melino
G
G
De Laurenzi
V
V
D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism; D002478:Cells, Cultured; D015536:Down-Regulation / Q000235:genetics; D006367:HeLa Cells; D006657:Histones / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016196:S Phase / Q000502:physiology*; D014158:Transcription, Genetic
D051017:Apoptosis Regulatory Proteins; C485604:CASP8AP2 protein, human; D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; D006657:Histones; C101693:NPAT protein, human; D009687:Nuclear Proteins; D012333:RNA, Messenger; C068921:p80-coilin