Histone gene transcription: A model for responsiveness to an integrated series of regulatory signals mediating cell cycle control and proliferation/differentiation interrelationships

Histone gene expression is restricted to the S-phase of the cell cycle. Control is at multiple levels and is mediated by the integration of regulatory signals in response to cell cycle progression and the onset of differentiation. The H4 gene promoter is organized into a series of independent and overlapping regulatory elements which exhibit selective, phosphorylation-dependent interactions with multiple transactivation factors. The three-dimensional organization of the promoter and, in particular, its chromatin structure, nucleosome organization, and interactions with the nuclear matrix may contribute to interrelationships of activities at multiple promoter elements. Molecular mechanisms are discussed that may participate in the coordinate expression of S-phase-specific core and H1 histone genes, together with other genes functionally coupled with DNA replication.