The histone subcode: poly(ADP-ribose) polymerase-1 (Parp-1) and Parp-2 control cell differentiation by regulating the transcriptional intermediary factor TIF1β and the heterochromatin protein HP1α Delphine Quénet * , Véronique Gasser * , Laetitia Fouillen ‡ , Florence Cammas † , Sarah Sanglier-Cianferani ‡ , Régine Losson † and Françoise Dantzer * ,1 * Département Intégrité du Génome, UMR7175, Ecole Supérieure de Biotechnologie de Strasbourg, Illkirch, France; † Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, France; and ‡ Laboratoire de Spectrométrie de Masse Bio-organique, UMR7178, Ecole de Chimie, Polymères et Matériaux, Strasbourg, France 1 Correspondence: Département IDG, UMR7175, ESBS, Bld. S. Brant, 67412 Illkirch, France. E-mail: fdantzer@esbs.u-strasbg.fr 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 (TIF1β) and the heterochromatin proteins (HP1) that affect endodermal differentiation. We show that Parp-2 binds to TIF1β with high affinity both directly and through HP1α. Both partners colocalize at pericentric heterochromatin in primitive endoderm-like cells. Parp-2 also binds to HP1β but not to HP1γ. In contrast Parp-1 binds weakly to TIF1β and HP1β only. Both Parps selectively poly(ADP-ribosyl)ate HP1α. 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 TIF1β to heterochromatic foci during primitive endodermal differentiation, Parp-1 and its activity modulate TIF1β-HP1α association with consequences on parietal endodermal differentiation. Both Parps control TIF1β transcriptional activity. In addition, this work identifies both Parps as new modulators of the HP1-mediated subcode histone.—Quénet, 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 TIF1β and the heterochromatin protein HP1α. Key Words: epigenetics • pericentric heterochromatin • post-translational modification • protein interactions
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The histone subcode: poly(ADP-ribose) polymerase-1 (Parp-1) and Parp-2 control cell differentiation by regulating the transcriptional intermediary factor TIF1β and the heterochromatin protein HP1α
Quénet, Delphine; Gasser, Véronique; Fouillen, Laetitia; Cammas, Florence; Sanglier-Cianferani, Sarah; Losson, Régine; Dantzer, Françoise
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, Volume 22 (11): 3853
Fed of American Socs for Experimental Biology – Nov 1, 2008
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