CDP/cut is the DNA-binding subunit of histone gene transcription factor HiNF-D: a mechanism for gene regulation at the G1/S phase cell cycle transition point independent of transcription factor E2F
Graduate School of Biomedical Sciences; Department of Cell Biology
Medical Subject Headings
Base Sequence; Binding Sites; *Carrier Proteins; *Cell Cycle; *Cell Cycle Proteins; Cell Nucleus; Consensus Sequence; DNA Footprinting; DNA Replication; DNA-Binding Proteins; E2F Transcription Factors; G1 Phase; Hela Cells; Histones; Homeodomain Proteins; Humans; Molecular Sequence Data; Mutagenesis, Site-Directed; Nuclear Proteins; *Promoter Regions (Genetics); Recombinant Fusion Proteins; Repressor Proteins; Restriction Mapping; S Phase; Transcription Factor DP1; Transcription Factors
Life Sciences | Medicine and Health Sciences
Transcription of the genes for the human histone proteins H4, H3, H2A, H2B, and H1 is activated at the G1/S phase transition of the cell cycle. We have previously shown that the promoter complex HiNF-D, which interacts with cell cycle control elements in multiple histone genes, contains the key cell cycle factors cyclin A, CDC2, and a retinoblastoma (pRB) protein-related protein. However, an intrinsic DNA-binding subunit for HiNF-D was not identified. Many genes that are up-regulated at the G1/S phase boundary are controlled by E2F, a transcription factor that associates with cyclin-, cyclin-dependent kinase-, and pRB-related proteins. Using gel-shift immunoassays, DNase I protection, and oligonucleotide competition analyses, we show that the homeodomain protein CDP/cut, not E2F, is the DNA-binding subunit of the HiNF-D complex. The HiNF-D (CDP/cut) complex with the H4 promoter is immunoreactive with antibodies against CDP/cut and pRB but not p107, whereas the CDP/cut complex with a nonhistone promoter (gp91-phox) reacts only with CDP and p107 antibodies. Thus, CDP/cut complexes at different gene promoters can associate with distinct pRB-related proteins. Transient coexpression assays show that CDP/cut modulates H4 promoter activity via the HiNF-D-binding site. Hence, DNA replication-dependent histone H4 genes are regulated by an E2F-independent mechanism involving a complex of CDP/cut with cyclin A/CDC2/ RB-related proteins.
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Citation: Proc Natl Acad Sci U S A. 1996 Oct 15;93(21):11516-21.
Proceedings of the National Academy of Sciences of the United States of America
Van Wijnen, Andre J.; van Gurp, Maria F.; De Ridder, Marleen C.; Tufarelli, Cristina; Last, Thomas J.; Birnbaum, Mark J.; Vaughan, Patricia S.; Giordano, Antonio; Wilhelm, Krek; Neufeld, Ellis J.; Stein, Janet L.; and Stein, Gary S., "CDP/cut is the DNA-binding subunit of histone gene transcription factor HiNF-D: a mechanism for gene regulation at the G1/S phase cell cycle transition point independent of transcription factor E2F" (1996). GSBS Student Publications. 1295.