TRANSCRIPTION OF HISTONE-H4, HISTONE-H3, AND HISTONE-H1 CELL-CYCLE GENES - PROMOTER FACTOR HINF-D CONTAINS CDC2, CYCLIN-A, AND AN RB-RELATED PROTEIN

Cell cycle-controlled human histone genes are coordinately expressed d uring S phase, and transcriptional regulation involves a series of tra ns-acting factors (HiNFs). The proliferation-specific factor HiNF-D in teracts with multiple recognition motifs in histone H4, H3, and H1 pro moters. Using gel shift immunoassays, we show that CDC2, cyclin A, and an RB-related protein are ubiquitous subunits of HiNF-D binding activ ity isolated from several cell types. HiNF-D levels in vivo are sensit ive to okadaic acid and staurosporine, indicating that HiNF-D activity and/or assembly is influenced by phosphorylation status, Thus, HiNF-D appears to be a multicomponent phosphoprotein that participates in co ordinate control of multiple histone H4, H3, and H1 genes during the c ell cycle. The presence of cell cycle mediators in the HiNF-D complex suggests linkage between transcriptional control of histones, enzymes involved in DNA synthesis, and the onset of DNA replication during the G(1)/S phase transition.