The histone subcode: poly(ADP-ribose) polymerase-1 (Parp-1) and Parp-2 control cell differentiation by regulating the transcriptional intermediary factor TIF1 beta and the heterochromatin protein HP1 alpha

[摘要] Recent advances reveal emerging unique functions of poly(ADP-ribose) polymerase-1 (Parp-1) and Parp-2 in heterochromatin integrity and cell differentiation. However, the chromatin-mediated molecular and cellular events involved remain elusive. Here we describe specific physical and functional interactions of Parp-1 and Parp-2 with the transcriptional intermediary factor (TIF1 beta) and the heterochromatin proteins (HP1) that affect endodermal differentiation. We show that Parp-2 binds to TIF1 beta with high affinity both directly and through HP1 alpha. Both partners colocalize at pericentric heterochromatin in primitive endoderm-like cells. Parp-2 also binds to HP1 beta but not to HP1 gamma. In contrast Parp-1 binds weakly to TIF1 beta and HP1 beta only. Both Parps selectively poly(ADP-ribosyl) ate HP1 alpha. Using shRNA approaches, we provide evidence for distinct participation of both Parps in endodermal differentiation. Whereas Parp-2 and its activity are required for the relocation of TIF1 beta to heterochromatic foci during primitive endodermal differentiation, Parp-1 and its activity modulate TIF1 beta-HP1 alpha association with consequences on parietal endodermal differentiation. Both Parps control TIF1 beta transcriptional activity. In addition, this work identifies both Parps as new modulators of the HP1-mediated subcode histone. -Quenet, D., Gasser, V., Fouillen, L., Cammas, F., Sanglier-Cianferani, S., Losson, R., Dantzer, F. The histone subcode: poly(ADP-ribose) polymerase-1 (Parp-1) and Parp-2 control cell differentiation by regulating the transcriptional intermediary factor TIF1 beta and the heterochromatin protein HP1 alpha. FASEB J. 22, 3853-3865 (2008)

[发布日期] 2008-11-01

[关键词] ZINC FINGER PROTEINS;FUNCTIONAL INTERACTION;DNA-REPAIR;HP1;EXPRESSION;INTERACTS;CHROMATIN;FAMILY;CONTRIBUTES;MAINTENANCE