New chaps in the histone chaperone arena

Abstract

Understanding exactly how chromatin is assembled is paramount to addressing how select histone modifications may be transmitted, a putative epigenetic process. In the June 15, 2010, issue of Genes & Development, Drané and colleagues (pp. 1253-1265) identified DAXX as a novel H3.3-specific chaperone. This finding, in the context of others published by Goldberg and colleagues in Cell and Sawatsubashi and colleagues (pp. 159-170) in the January 15, 2010, issue of Genes & Development, provides the impetus for uncovering the mechanistic and functional properties of alternative histone deposition pathways.

Figure 1.

Sequence alignment of human canonical H3 variants. No substitutions are found within key residues known to facilitate transcriptional silencing or activation. Changes in amino acid composition are highlighted in blue. Modifications generally correlating with active transcription are shown in green, and those correlating with silenced chromatin are shown in red.

Figure 2.

During RC assembly, the ASF1 chaperone is thought to transfer newly synthesized soluble H3.1–H4 dimers to CAF-1 through direct interactions with its p60 subunit (Tyler et al. 2001; Mello et al. 2002). CAF-1 would then facilitate the assembly of a central (H3.1–H4)₂ tetramer to which two H2A–H2B dimers are juxtaposed by other chaperones to complete a core nucleosomal unit. Similarly, during RI chromatin assembly, ASF1-bound H3.3–H4 would be transferred to HIRA for tetramer formation (Green et al. 2005). Note, however, that the deposition of H3.3 in the Drosophila male pronucleus is HIRA-dependent, but ASF1-independent (Bonnefoy et al. 2007) in the histone-rich fertilized egg. Novel alternate pathways for H3.3–H4 deposition include the DAXX chaperone coupled to the ATRX ATP-dependent chromatin remodeler (Drané et al. 2010; Goldberg et al. 2010), as well as targeted H3.3 deposition to regulatory elements by DEK (Sawatsubashi et al. 2010). Boxes highlight queries to consider in future studies.

Figure 3.

Model of H3.3 deposition by HIRA, DAXX, and DEK. HIRA deposits H3.3 within the coding region of transcribed genes, but also at the transcription start site (TSS) of both active and repressed high-CpG content genes in ESCs. Likewise, ATRX directs DAXX-mediated H3.3 deposition to telomeres in ESCs, but also to pericentric heterochromatin. In Drosophila, phosphorylated DEK associates with the ecdysone receptor and acts as a coactivator. The H3.3 Ser 31 is phosphorylated in metaphase (Hake et al. 2005; Wong et al. 2009).