Two Distinct Nucleosome Assembly Pathways: Dependent or Independent of DNA Synthesis Promoted by Histone H3.1 and H3.3 Complexes (original) (raw)

  1. Y. NAKATANI,
  2. D. RAY-GALLET,
  3. J.-P. QUIVY,
  4. H. TAGAMI, and
  5. G. ALMOUZNI
  6. * Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115; † Section de Recherche, Institut Curie, UMR 218 du CNRS, 75248 Paris Cedex 05, France

Excerpt

Covalent modifications of histones, such as acetylation, phosphorylation, and methylation, have been shownto contribute to the formation and maintenance of transcriptionally active and inactive chromatin (Jenuwein andAllis 2001; Grewal and Elgin 2002; Turner 2002; Felsenfeld and Groudine 2003; Kurdistani and Grunstein 2003).In addition to histone modifications, histone variants thatmark specific chromatin loci could play important rolesin formation and maintenance of epigenetic memory(Henikoff et al. 2004). In mammals, three isotypes of histone H3 (H3.1, H3.2, and H3.3) have been identified inaddition to the centromere-specific histone H3 variant,CENP-A. Histone H3.1 is the major histone H3, which ispredominantly synthesized and assembled in nucleosomes during S phase. Histone H3.2 is closely related toH3.1 and has been shown to belong to the family of Sphase subtypes (Franklin and Zweidler 1977). In contrastto H3.1 and H3.2, H3.3 is expressed in proliferating cellsat all stages of the cell cycle as well as in quiescent cells(Wu et al. 1982). This latter observation is consistent withthe fact that H3.3 can be incorporated into nucleosomesin the absence of DNA synthesis. Given these properties,H3.3-H4 has been suggested to replace H3-H4 in nucleosomes, in particular during transcriptional activation (Ahmad and Henikoff 2002; Henikoff et al. 2004). Although,we are only at an early stage in our understanding of thefunctional role of these histone variants, it is clear thattheir mode of incorporation represents a crucial eventwith major implications for cell fate and stability of expression programs. In this context, it is remarkable to realize that while the principles for a mechanism to ensurethe faithful propagation of genetic information throughDNA replication were discovered a half-century ago(Watson and Crick 1953), the molecular events leading tothe maintenance and transmission of epigenetic information remain a real puzzle. Much of our knowledge concerning chromatin assembly and nucleosome formationhas dealt so far mainly with bulk histones (Verreault2000; Mello and Almouzni 2001), and the issue of how todeal with histone variants, in particular H3, has remaine...