Transcription of histone H4, H3, and 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 during S phase, and transcriptional regulation involves a series of trans-acting factors (HiNFs). The proliferation-specific factor HiNF-D interacts with multiple recognition motifs in histone H4, H3, and H1 promoters. Using gel shift immunoassays, we show that CDC2, cyclin A, and an RB-related protein are ubiquitous subunits of HiNF-D binding activity isolated from several cell types. HiNF-D levels in vivo are sensitive 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 coordinate control of multiple histone H4, H3, and H1 genes during the cell 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 G1/S phase transition.
van Wijnen
A J
AJ
Department of Cell Biology, University of Massachusetts Medical School and Cancer Center, Worcester 01655.
Aziz
F
F
Graña
X
X
De Luca
A
A
Desai
R K
RK
Jaarsveld
K
K
Last
T J
TJ
Soprano
K
K
Giordano
A
A
Lian
J B
JB
D000470:Alkaloids / Q000494:pharmacology; D001483:Base Sequence; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002453:Cell Cycle; D016213:Cyclins / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D004988:Ethers, Cyclic / Q000494:pharmacology; D005786:Gene Expression Regulation; D006657:Histones / Q000235:genetics*; D006801:Humans; D066298:In Vitro Techniques; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D019319:Okadaic Acid; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D016160:Retinoblastoma Protein / Q000737:chemistry; D019311:Staurosporine; D014157:Transcription Factors / Q000737:chemistry*; D014158:Transcription, Genetic; D015533:Transcriptional Activation
D000470:Alkaloids; D016213:Cyclins; D004268:DNA-Binding Proteins; D004988:Ethers, Cyclic; D006657:Histones; D046911:Macromolecular Substances; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D016160:Retinoblastoma Protein; D014157:Transcription Factors; D019319:Okadaic Acid; D016203:CDC2 Protein Kinase; D019311:Staurosporine