title: Chromatin dynamics during epigenetic reprogramming in the mouse germ line.
abstract: A unique feature of the germ cell lineage is the generation of totipotency. A critical event in this context is DNA demethylation and the erasure of parental imprints in mouse primordial germ cells (PGCs) on embryonic day 11.5 (E11.5) after they enter into the developing gonads. Little is yet known about the mechanism involved, except that it is apparently an active process. We have examined the associated changes in the chromatin to gain further insights into this reprogramming event. Here we show that the chromatin changes occur in two steps. The first changes in nascent PGCs at E8.5 establish a distinctive chromatin signature that is reminiscent of pluripotency. Next, when PGCs are residing in the gonads, major changes occur in nuclear architecture accompanied by an extensive erasure of several histone modifications and exchange of histone variants. Furthermore, the histone chaperones HIRA and NAP-1 (NAP111), which are implicated in histone exchange, accumulate in PGC nuclei undergoing reprogramming. We therefore suggest that the mechanism of histone replacement is critical for these chromatin rearrangements to occur. The marked chromatin changes are intimately linked with genome-wide DNA demethylation. On the basis of the timing of the observed events, we propose that if DNA demethylation entails a DNA repair-based mechanism, the evident histone replacement would represent a repair-induced response event rather than being a prerequisite.
authors: Wellcome Trust/Cancer Research UK Gurdon Institute of Cancer and Developmental Biology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QN, UK.
authors: Petra
authors: P
authors: Hajkova
authors: Wellcome Trust/Cancer Research UK Gurdon Institute of Cancer and Developmental Biology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QN, UK.
authors: Katia
authors: K
authors: Ancelin
authors: Max-Planck-Institute of Immunobiology, Stuebeweg 51, 79108 Freiburg, Germany.
authors: Tanja
authors: T
authors: Waldmann
authors: CNRS/Institute Curie, 26 rue d'Ulm, 75248 Paris Cedex 05, France.
authors: Nicolas
authors: N
authors: Lacoste
authors: Wellcome Trust/Cancer Research UK Gurdon Institute of Cancer and Developmental Biology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QN, UK.
authors: Ulrike C
authors: UC
authors: Lange
authors: Wellcome Trust/Cancer Research UK Gurdon Institute of Cancer and Developmental Biology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QN, UK.
authors: Francesca
authors: F
authors: Cesari
authors: Wellcome Trust/Cancer Research UK Gurdon Institute of Cancer and Developmental Biology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QN, UK.
authors: Caroline
authors: C
authors: Lee
authors: CNRS/Institute Curie, 26 rue d'Ulm, 75248 Paris Cedex 05, France.
authors: Genevieve
authors: G
authors: Almouzni
authors: Max-Planck-Institute of Immunobiology, Stuebeweg 51, 79108 Freiburg, Germany.
authors: Robert
authors: R
authors: Schneider
authors: Wellcome Trust/Cancer Research UK Gurdon Institute of Cancer and Developmental Biology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QN, UK.
authors: M Azim
authors: MA
authors: Surani
mesh_terms: D000818:Animals; D002843:Chromatin / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005854:Germ Cells / Q000378:metabolism*; D006066:Gonads / Q000166:cytology / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D051379:Mice; D013234:Stem Cells / Q000378:metabolism
chemical_list: D002843:Chromatin; D006657:Histones