Replication-Independent Histone Deposition by the HIR Complex and Asf1

Abstract

The orderly deposition of histones onto DNA is mediated by conserved assembly complexes, including chromatin assembly factor-1 (CAF-1) and the Hir proteins . CAF-1 and the Hir proteins operate in distinct but functionally overlapping histone deposition pathways in vivo . The Hir proteins and CAF-1 share a common partner, the highly conserved histone H3/H4 binding protein Asf1, which binds the middle subunit of CAF-1 as well as to Hir proteins . Asf1 binds to newly synthesized histones H3/H4 , and this complex stimulates histone deposition by CAF-1 . In yeast, Asf1 is required for the contribution of the Hir proteins to gene silencing . Here, we demonstrate that Hir1, Hir2, Hir3, and Hpc2 comprise the HIR complex, which copurifies with the histone deposition protein Asf1. Together, the HIR complex and Asf1 deposit histones onto DNA in a replication-independent manner. Histone deposition by the HIR complex and Asf1 is impaired by a mutation in Asf1 that inhibits HIR binding. These data indicate that the HIR complex and Asf1 proteins function together as a conserved eukaryotic pathway for histone replacement throughout the cell cycle.

Remodeling of chromatin structure in senescent cells and its potential impact on tumor suppression and aging

“…In vitro, HIRA has been shown to act as a histone chaperone, preferentially depositing the histone variant histone H3.3 into nucleosomes, compared to canonical histone H3.1 (49,72,100,102,125). Consistent with their partially overlapping functions, Asf1 and Hir proteins physically interact and in yeast this interaction is necessary for telomeric silencing (32,49,116).…”

Regulation of Histone Gene Expression in Budding Yeast

“…The Hir1, Hir2, Hir3, and Hpc2 proteins together form the HIR complex, which acts as a histone chaperone (Green et al 2005;Prochasson et al 2005). Another histone chaperone, Asf1, is associated with the HIR complex (Green et al 2005).…”

“…The Hir1, Hir2, Hir3, and Hpc2 proteins together form the HIR complex, which acts as a histone chaperone (Green et al 2005;Prochasson et al 2005). Another histone chaperone, Asf1, is associated with the HIR complex (Green et al 2005). Null mutants in components of the HIR complex do not have a growth phenotype (Sherwood et al 1993), but asf1D cells grow poorly (Le et al 1997).…”

“…Rather confusingly, the HIR complex is involved in diverse processes in addition to histone gene regulation, apparently acting as a histone chaperone in replication-independent nucleosome assembly (Green et al 2005;Prochasson et al 2005), GAL transcript elongation by RNA polymerase II (Nourani et al 2006), heterochromatin silencing (Sharp et al 2001), and kinetochore function (Sharp et al 2002). Thus, the HIR complex is not a specific repressor for the histone genes.…”

“…Rtt106 was identified as a repressor of HTA1 expression in a genetic screen, which also identified two other histone chaperones as repressors: the HIR complex and Asf1 (Fillingham et al 2009). Thus, three different histone chaperones are involved, although physical interactions between all of them have been reported in vitro and in vivo (Sutton et al 2001;Green et al 2005;Fillingham et al 2009;Ferreira et al 2011), suggesting that they might act together, with apparently redundant functions. The HTA1-HTB1 promoter is more depleted of nucleosomes in rtt106D and hir1D cells than in wild-type cells, suggesting that these chaperones might facilitate assembly of nucleosomes on the histone promoters, which then repress transcription (Fillingham et al 2009).…”