Histone Acetylation and Chromatin Assembly: A Single Escort, Multiple Dances?

The compaction of eukaryotic DNA into chromatin directly affects transmission of genetic material to daughter cells as well as the establishment of specific patterns of gene expression. How chromatin assembly is achieved and regulated in vivo is still largely a mystery. The fundamental building block of chromatin is the nucleosome, which is comprised of an octamer of histone proteins (two molecules each of histones H2A, H2B, H3, and H4) and 146 base pairs of DNA wound around the octamer. Histone synthesis and nucleosome assembly are closely tied to DNA replication in most cells, but how these processes are coupled is not clear. In this issue of Cell, Stillman and colleagues (Verreault et al. 1996, this issue) describe the isolation of a Chromatin Assembly Complex (CAC) from nuclei of human cells which assembles nucleosomes in a replication-dependent manner. Interestingly, CAC consists of the previously identified, three-subunit Chromatin Assembly Factor 1 (CAF-1), H3, and specific acetylated isoforms of H4. Also in this issue, Gottschling and coworkers (Parthun et al. 1996, this issue) describe the identification of a yeast histone acetyltransferase complex of the B type (HAT B, see below) likely to establish the acetylation pattern associated with deposition of nascent H4 into chromatin. Surprisingly, the yeast HAT B complex and the human CAF-1 complex contain structurally related 48 kDa subunits, providing a direct molecular link between histone acetylation and chromatin assembly. Moreover, human p48 has been isolated previously in association with a histone deacetylase (HD1) (Taunton et al. 1996) and the Retinoblastoma (Rb) tumor suppressor protein (Qian et al. 1995) and has therefore acquired the name RbAp48. Together these findings indicate that histone acetylation, deacetylation, and chromatin assembly may be coordinated through common p48 subunits, and that p48 or other factors involved in these processes may provide unique targets for the regulation of cell proliferation.