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PMID: 8876167 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.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.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 93 ·No. 21 ·1996-10-15 ·Pages 11516-21

van Wijnen AJ, van Gurp MF, de Ridder MC, Tufarelli C, Last TJ, Birnbaum M, Vaughan PS, Giordano A, Krek W, Neufeld EJ, Stein JL, Stein GS

Abstract

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.

MeSH Terms
Base Sequence Binding Sites Carrier Proteins Cell Cycle Cell Cycle Proteins Cell Nucleus/metabolism Consensus Sequence DNA Footprinting DNA Replication DNA-Binding Proteins/metabolism E2F Transcription Factors G1 Phase HeLa Cells Histones/biosynthesis,genetics Homeodomain Proteins Humans Molecular Sequence Data Mutagenesis, Site-Directed Nuclear Proteins/metabolism Promoter Regions, Genetic Recombinant Fusion Proteins/metabolism Repressor Proteins/metabolism Restriction Mapping Retinoblastoma-Binding Protein 1 S Phase Transcription Factor DP1 Transcription Factors/metabolism
Chemicals
CUX1 protein, human Carrier Proteins Cell Cycle Proteins DNA-Binding Proteins E2F Transcription Factors HINF-D protein, human Histones Homeodomain Proteins Nuclear Proteins Recombinant Fusion Proteins Repressor Proteins Retinoblastoma-Binding Protein 1 Transcription Factor DP1 Transcription Factors
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
van Wijnen A J
Department of Cell Biology, University of Massachusetts Medical School, Worcester 01655, USA.
van Gurp M F
de Ridder M C
Tufarelli C
Last T J
Birnbaum M
Vaughan P S
Giordano A
Krek W
Neufeld E J
Stein J L
Stein G S
References (48)
48 references, click to expand
  1. DP and E2F proteins: coordinating transcription with cell cycle progression.
    Curr Opin Cell Biol. 1994 Dec;6(6):859-66 PMID: 7880534
  2. The E2F transcription factor activates a replication-dependent human H2A gene in early S phase of the cell cycle.
    Mol Cell Biol. 1996 May;16(5):1889-95 PMID: 8628255
  3. Human CCAAT displacement protein is homologous to the Drosophila homeoprotein, cut.
    Nat Genet. 1992 Apr;1(1):50-5 PMID: 1301999
  4. Delineation of a human histone H4 cell cycle element in vivo: the master switch for H4 gene transcription.
    Proc Natl Acad Sci U S A. 1994 May 10;91(10):4475-9 PMID: 8183933
  5. Protein-DNA interactions in vivo upstream of a cell cycle-regulated human H4 histone gene.
    Science. 1987 Jun 5;236(4806):1308-11 PMID: 3035717
  6. Cell-cycle regulation of a human histone H2b gene is mediated by the H2b subtype-specific consensus element.
    Genes Dev. 1988 Jan;2(1):32-9 PMID: 3128460
  7. G1/S-regulated E2F-containing protein complexes bind to the mouse thymidine kinase gene promoter.
    J Biol Chem. 1994 Jan 14;269(2):1306-13 PMID: 8288595
  8. Human H4 histone gene transcription requires the proliferation-specific nuclear factor HiNF-D. Auxiliary roles for HiNF-C (Sp1-like) and HiNF-A (high mobility group-like).
    J Biol Chem. 1989 Sep 5;264(25):15034-42 PMID: 2768251
  9. Functional role for Sp1 in the transcriptional amplification of a cell cycle regulated histone H4 gene.
    Biochemistry. 1995 Jun 13;34(23):7648-58 PMID: 7779811
  10. E2F: a link between the Rb tumor suppressor protein and viral oncoproteins.
    Science. 1992 Oct 16;258(5081):424-9 PMID: 1411535
  11. CCAAT displacement protein as a repressor of the myelomonocytic-specific gp91-phox gene promoter.
    J Biol Chem. 1991 Sep 5;266(25):16736-44 PMID: 1885602
  12. Histone H2B gene transcription during Xenopus early development requires functional cooperation between proteins bound to the CCAAT and octamer motifs.
    Mol Cell Biol. 1992 Oct;12(10):4400-11 PMID: 1406629
  13. The retinoblastoma protein and cell cycle control.
    Cell. 1995 May 5;81(3):323-30 PMID: 7736585
  14. The role of cellular transcription factor E2F in the regulation of cdc2 mRNA expression and cell cycle control of human hematopoietic cells.
    J Biol Chem. 1994 Oct 21;269(42):26249-58 PMID: 7929342
  15. Purification of the human histone H4 gene-specific transcription factors H4TF-1 and H4TF-2.
    Genes Dev. 1988 Dec;2(12B):1700-12 PMID: 3071490
  16. Transcriptional element H4-site II of cell cycle regulated human H4 histone genes is a multipartite protein/DNA interaction site for factors HiNF-D, HiNF-M, and HiNF-P: involvement of phosphorylation.
    J Cell Biochem. 1991 Jun;46(2):174-89 PMID: 1655821
  17. A new bipartite DNA-binding domain: cooperative interaction between the cut repeat and homeo domain of the cut homeo proteins.
    Genes Dev. 1994 Jan;8(2):245-57 PMID: 7905452
  18. Regulation of cyclin D1, DNA topoisomerase I, and proliferating cell nuclear antigen promoters during the cell cycle.
    Gene Expr. 1995;4(3):95-109 PMID: 7734951
  19. The retinoblastoma protein as a transcriptional repressor.
    Trends Cell Biol. 1993 Feb;3(2):43-6 PMID: 14731718
  20. Cell-cycle regulation of human B-myb transcription.
    Gene. 1995 Jul 28;160(2):277-81 PMID: 7642110
  21. Cellular targets for activation by the E2F1 transcription factor include DNA synthesis- and G1/S-regulatory genes.
    Mol Cell Biol. 1995 Aug;15(8):4215-24 PMID: 7623816
  22. G1 phase progression: cycling on cue.
    Cell. 1994 Nov 18;79(4):551-5 PMID: 7954821
  23. Concerted control of multiple histone promoter factors during cell density inhibition of proliferation in osteosarcoma cells: reciprocal regulation of cell cycle-controlled and bone-related genes.
    Cancer Res. 1993 May 15;53(10 Suppl):2399-409 PMID: 8485727
  24. Activation of a cell-cycle-regulated histone gene by the oncogenic transcription factor IRF-2.
    Nature. 1995 Sep 28;377(6547):362-5 PMID: 7566094
  25. E2F-dependent regulation of human MYC: trans-activation by cyclins D1 and A overrides tumour suppressor protein functions.
    Oncogene. 1994 Jul;9(7):2029-36 PMID: 8208548
  26. DNA-binding specificity of the cut repeats from the human cut-like protein.
    Mol Cell Biol. 1995 Jan;15(1):129-40 PMID: 7799919
  27. The regulation of histone synthesis in the cell cycle.
    Annu Rev Biochem. 1991;60:827-61 PMID: 1883210
  28. Tumor cells exhibit deregulation of the cell cycle histone gene promoter factor HiNF-D.
    Science. 1990 Mar 23;247(4949 Pt 1):1454-7 PMID: 2321007
  29. Correlation between E2F-1 requirement in the S phase and E2F-1 transactivation of cell cycle-related genes in human cells.
    Cancer Res. 1994 Mar 15;54(6):1402-6 PMID: 8137237
  30. Overlapping and CpG methylation-sensitive protein-DNA interactions at the histone H4 transcriptional cell cycle domain: distinctions between two human H4 gene promoters.
    Mol Cell Biol. 1992 Jul;12(7):3273-87 PMID: 1620129
  31. Transcription of histone H4, H3, and H1 cell cycle genes: promoter factor HiNF-D contains CDC2, cyclin A, and an RB-related protein.
    Proc Natl Acad Sci U S A. 1994 Dec 20;91(26):12882-6 PMID: 7809140
  32. Cytokine induction of proliferation and expression of CDC2 and cyclin A in FDC-P1 myeloid hematopoietic progenitor cells: regulation of ubiquitous and cell cycle-dependent histone gene transcription factors.
    J Cell Biochem. 1995 Nov;59(3):291-302 PMID: 8567748
  33. Human H1 histone gene promoter CCAAT box binding protein HiNF-B is a mosaic factor.
    Biochemistry. 1988 Aug 23;27(17):6534-41 PMID: 3219352
  34. Transcription from TATA-less promoters: dihydrofolate reductase as a model.
    Crit Rev Eukaryot Gene Expr. 1993;3(4):229-54 PMID: 8286846
  35. A 60 kd cdc2-associated polypeptide complexes with the E1A proteins in adenovirus-infected cells.
    Cell. 1989 Sep 8;58(5):981-90 PMID: 2570639
  36. Interaction of the CCAAT displacement protein with shared regulatory elements required for transcription of paired histone genes.
    Mol Cell Biol. 1995 Jul;15(7):3587-96 PMID: 7791766
  37. Regulation of the mouse histone H2A.X gene promoter by the transcription factor E2F and CCAAT binding protein.
    J Biol Chem. 1995 Aug 11;270(32):18759-65 PMID: 7642525
  38. Histone gene transcription: a model for responsiveness to an integrated series of regulatory signals mediating cell cycle control and proliferation/differentiation interrelationships.
    J Cell Biochem. 1994 Apr;54(4):393-404 PMID: 8014188
  39. Temporal regulation of cyclin A-p107 and p33cdk2 complexes binding to a human thymidine kinase promoter element important for G1-S phase transcriptional regulation.
    Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3554-8 PMID: 8475104
  40. Negative regulation of the growth-promoting transcription factor E2F-1 by a stably bound cyclin A-dependent protein kinase.
    Cell. 1994 Jul 15;78(1):161-72 PMID: 8033208
  41. Cell cycle controlled histone H1, H3, and H4 genes share unusual arrangements of recognition motifs for HiNF-D supporting a coordinate promoter binding mechanism.
    J Cell Physiol. 1994 Jun;159(3):515-30 PMID: 8188766
  42. Transcriptional regulation of the dihydrofolate reductase/rep-3 locus.
    Crit Rev Eukaryot Gene Expr. 1994;4(1):19-53 PMID: 7987046
  43. Principles of CDK regulation.
    Nature. 1995 Mar 9;374(6518):131-4 PMID: 7877684
  44. H1TF2A, the large subunit of a heterodimeric, glutamine-rich CCAAT-binding transcription factor involved in histone H1 cell cycle regulation.
    Mol Cell Biol. 1994 Dec;14(12):8322-32 PMID: 7969168
  45. Mutually exclusive interaction of the CCAAT-binding factor and of a displacement protein with overlapping sequences of a histone gene promoter.
    Cell. 1987 Jul 31;50(3):347-59 PMID: 3607873
  46. Antibodies specific for the human retinoblastoma protein identify a family of related polypeptides.
    Mol Cell Biol. 1991 Nov;11(11):5792-9 PMID: 1717832
  47. Sequence-specific DNA binding of individual cut repeats of the human CCAAT displacement/cut homeodomain protein.
    Proc Natl Acad Sci U S A. 1994 Aug 2;91(16):7757-61 PMID: 7914370
  48. Repressor activity of CCAAT displacement protein in HL-60 myeloid leukemia cells.
    J Biol Chem. 1995 May 26;270(21):12745-50 PMID: 7759529
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.93.21.11516
Published
1996-10-15
Pages
11516-21
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC38089
Subset
IM
Grants
NIAMS NIH HHS · AR 39588 · United States
NCI NIH HHS · CA 60999 · United States
NIGMS NIH HHS · GM 32010 · United States
External Links
PubMed source DOI: 10.1073/pnas.93.21.11516 PMC Full Text View journal details
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