Involvement of ZFPIP/Zfp462 in chromatin integrity and survival of P19 pluripotent cells.
Toti- or pluripotent cells proliferation and/or differentiation have been shown to be strongly related to nuclear chromatin organization and structure over the last past years. We have recently identified ZFPIP/Zfp462 as a zinc finger nuclear factor necessary for correct cell division during early embryonic developmental steps of vertebrates. We thus questioned whether this factor was playing a general role during cell division or if it was somehow involved in embryonic cell fate or differentiation. To achieve this goal, we performed a knock-down experiment in the pluripotent P19 and differentiated 3T3 cell lines, both expressing endogenous ZFPIP/Zfp462. Using specific shRNA directed against ZFPIP/Zfp462 transcripts, we demonstrated that depletion of this protein induced cell death in P19 but had no effect in 3T3 cells. In addition, in the absence of the protein, the P19 cells exhibited a complete destructuration of pericentromeric domains associated with a redistribution of the HP1alpha proteins and an increase in DNA satellites transcribed RNAs level. These data suggested an instrumental role of ZFPIP/Zfp462 in maintaining the chromatin structure of pluripotent cells.
Massé
Julie
J
UMR CNRS 6061, Institut of Génétique et Développement de Rennes (IGDR), Faculté de Médecine, Université de Rennes 1, Rennes, France.
Laurent
Audrey
A
Nicol
Barbara
B
Guerrier
Daniel
D
Pellerin
Isabelle
I
Deschamps
Stéphane
S
D016475:3T3 Cells; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D019556:COS Cells; D002352:Carrier Proteins / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D002843:Chromatin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D043171:Chromosomal Instability / Q000235:genetics / Q000502:physiology; D004268:DNA-Binding Proteins; D004622:Embryo, Mammalian; D005786:Gene Expression Regulation / Q000187:drug effects; D051379:Mice; D009419:Nerve Tissue Proteins / Q000502:physiology*; D039904:Pluripotent Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D034741:RNA, Small Interfering / Q000494:pharmacology
D002352:Carrier Proteins; D002843:Chromatin; D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; C519662:Zfp462 protein, mouse