Skip to main content
NCBI home page
Nucleic Acids Research logoLink to Nucleic Acids Research
. 1996 Feb 1;24(3):523–531. doi: 10.1093/nar/24.3.523

Identification of a second conserved element within the coding sequence of a mouse H3 histone gene that interacts with nuclear factors and is necessary for normal expression.

N K Kaludov 1, L Pabón-Peña 1, M M Hurt 1
PMCID: PMC145646  PMID: 8602367

Abstract

Replication-dependent histone genes of all four nucleosomal classes are coordinately up-regulated at the beginning of S phase of the eukaryotic cell cycle. The universality and importance of this process in eukaryotic cells suggest that common regulatory mechanisms are involved in controlling the high level of expression of these histone genes. We have previously identified the alpha element within mouse H2a.2 and H3.2 coding region activating sequences (CRAS), which is involved in regulation of these two replication-dependent genes. Here we report the identification of a second element within the mouse histone CRAS, the omega element. This element interacts with nuclear proteins and we present in vivo evidence that this sequence is required for normal expression. Omega nucleotides involved in interaction with nuclear proteins have been precisely mapped by menas of DNase I footprinting and methylation interference assays. A naturally occurring mutation in the omega sequence is found in a replication-independent H3.3 gene. Mutation of the H3.2 omega element to that of the H3.3 sequence (3 nt changes) caused a 4-fold drop in in vivo expression of the H3.2 gene in stably transfected CHO cells, equally the effect of mutation of all 7 nt of the element. By UV cross-linking we have determined the approximate molecular weight of the omega binding protein to be 45 kDa. Finally, we identify putative omega sequences in the coding region of mouse H2B and H4 histone genes.

Full Text

The Full Text of this article is available as a PDF (172.5 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Birnbaum M. J., Wright K. L., van Wijnen A. J., Ramsey-Ewing A. L., Bourke M. T., Last T. J., Aziz F., Frenkel B., Rao B. R., Aronin N. Functional role for Sp1 in the transcriptional amplification of a cell cycle regulated histone H4 gene. Biochemistry. 1995 Jun 13;34(23):7648–7658. doi: 10.1021/bi00023a011. [DOI] [PubMed] [Google Scholar]
  2. Butler W. B., Mueller G. C. Control of histone synthesis in HeLa cells. Biochim Biophys Acta. 1973 Feb 4;294(1):481–496. doi: 10.1016/0005-2787(73)90104-4. [DOI] [PubMed] [Google Scholar]
  3. Chaney W. G., Howard D. R., Pollard J. W., Sallustio S., Stanley P. High-frequency transfection of CHO cells using polybrene. Somat Cell Mol Genet. 1986 May;12(3):237–244. doi: 10.1007/BF01570782. [DOI] [PubMed] [Google Scholar]
  4. Chodosh L. A., Carthew R. W., Sharp P. A. A single polypeptide possesses the binding and transcription activities of the adenovirus major late transcription factor. Mol Cell Biol. 1986 Dec;6(12):4723–4733. doi: 10.1128/mcb.6.12.4723. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  6. Eilers A., Bouterfa H., Triebe S., Doenecke D. Role of a distal promoter element in the S-phase control of the human H1.2 histone gene transcription. Eur J Biochem. 1994 Jul 15;223(2):567–574. doi: 10.1111/j.1432-1033.1994.tb19026.x. [DOI] [PubMed] [Google Scholar]
  7. Gilman M. Z., Wilson R. N., Weinberg R. A. Multiple protein-binding sites in the 5'-flanking region regulate c-fos expression. Mol Cell Biol. 1986 Dec;6(12):4305–4316. doi: 10.1128/mcb.6.12.4305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Graves R. A., Marzluff W. F. Rapid reversible changes in the rate of histone gene transcription and histone mRNA levels in mouse myeloma cells. Mol Cell Biol. 1984 Feb;4(2):351–357. doi: 10.1128/mcb.4.2.351. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Groppi V. E., Jr, Coffino P. G1 and S phase mammalian cells synthesize histones at equivalent rates. Cell. 1980 Aug;21(1):195–204. doi: 10.1016/0092-8674(80)90127-0. [DOI] [PubMed] [Google Scholar]
  10. Heintz N., Sive H. L., Roeder R. G. Regulation of human histone gene expression: kinetics of accumulation and changes in the rate of synthesis and in the half-lives of individual histone mRNAs during the HeLa cell cycle. Mol Cell Biol. 1983 Apr;3(4):539–550. doi: 10.1128/mcb.3.4.539. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Heintz N. The regulation of histone gene expression during the cell cycle. Biochim Biophys Acta. 1991 Mar 26;1088(3):327–339. doi: 10.1016/0167-4781(91)90122-3. [DOI] [PubMed] [Google Scholar]
  12. Hillel Z., Wu C. W. Photochemical cross-linking studies on the interaction of Escherichia coli RNA polymerase with T7 DNA. Biochemistry. 1978 Jul 25;17(15):2954–2961. doi: 10.1021/bi00608a003. [DOI] [PubMed] [Google Scholar]
  13. Hraba-Renevey S., Kress M. Expression of a mouse replacement histone H3.3 gene with a highly conserved 3' noncoding region during SV40- and polyoma-induced Go to S-phase transition. Nucleic Acids Res. 1989 Apr 11;17(7):2449–2461. doi: 10.1093/nar/17.7.2449. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hurt M. M., Bowman T. L., Marzluff W. F. A common transcriptional activator is located in the coding region of two replication-dependent mouse histone genes. Mol Cell Biol. 1991 Jun;11(6):2929–2936. doi: 10.1128/mcb.11.6.2929. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hurt M. M., Chodchoy N., Marzluff W. F. The mouse histone H2a.2 gene from chromosome 3. Nucleic Acids Res. 1989 Nov 11;17(21):8876–8876. doi: 10.1093/nar/17.21.8876. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hurt M. M., Pandey N. B., Marzluff W. F. A region in the coding sequence is required for high-level expression of murine histone H3 gene. Proc Natl Acad Sci U S A. 1989 Jun;86(12):4450–4454. doi: 10.1073/pnas.86.12.4450. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Krieg P. A., Melton D. A. In vitro RNA synthesis with SP6 RNA polymerase. Methods Enzymol. 1987;155:397–415. doi: 10.1016/0076-6879(87)55027-3. [DOI] [PubMed] [Google Scholar]
  18. Krimer D. B., Cheng G., Skoultchi A. I. Induction of H3.3 replacement histone mRNAs during the precommitment period of murine erythroleukemia cell differentiation. Nucleic Acids Res. 1993 Jun 25;21(12):2873–2879. doi: 10.1093/nar/21.12.2873. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kunkel T. A., Roberts J. D., Zakour R. A. Rapid and efficient site-specific mutagenesis without phenotypic selection. Methods Enzymol. 1987;154:367–382. doi: 10.1016/0076-6879(87)54085-x. [DOI] [PubMed] [Google Scholar]
  20. La Bella F., Heintz N. Histone gene transcription factor binding in extracts of normal human cells. Mol Cell Biol. 1991 Dec;11(12):5825–5831. doi: 10.1128/mcb.11.12.5825. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Levine B. J., Liu T. J., Marzluff W. F., Skoultchi A. I. Differential expression of individual members of the histone multigene family due to sequences in the 5' and 3' regions of the genes. Mol Cell Biol. 1988 May;8(5):1887–1895. doi: 10.1128/mcb.8.5.1887. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Lin S. Y., Riggs A. D. Photochemical attachment of lac repressor to bromodeoxyuridine-substituted lac operator by ultraviolet radiation. Proc Natl Acad Sci U S A. 1974 Mar;71(3):947–951. doi: 10.1073/pnas.71.3.947. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Maxam A. M., Gilbert W. Sequencing end-labeled DNA with base-specific chemical cleavages. Methods Enzymol. 1980;65(1):499–560. doi: 10.1016/s0076-6879(80)65059-9. [DOI] [PubMed] [Google Scholar]
  24. Meier V. S., Böhni R., Schümperli D. Nucleotide sequence of two mouse histone H4 genes. Nucleic Acids Res. 1989 Jan 25;17(2):795–795. doi: 10.1093/nar/17.2.795. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Osley M. A. The regulation of histone synthesis in the cell cycle. Annu Rev Biochem. 1991;60:827–861. doi: 10.1146/annurev.bi.60.070191.004143. [DOI] [PubMed] [Google Scholar]
  26. Pauli U., Chrysogelos S., Stein G., Stein J., Nick H. Protein-DNA interactions in vivo upstream of a cell cycle-regulated human H4 histone gene. Science. 1987 Jun 5;236(4806):1308–1311. doi: 10.1126/science.3035717. [DOI] [PubMed] [Google Scholar]
  27. Plumb M., Stein J., Stein G. Coordinate regulation of multiple histone mRNAs during the cell cycle in HeLa cells. Nucleic Acids Res. 1983 Apr 25;11(8):2391–2410. doi: 10.1093/nar/11.8.2391. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Ramsey-Ewing A., Van Wijnen A. J., Stein G. S., Stein J. L. 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):4475–4479. doi: 10.1073/pnas.91.10.4475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Shapiro D. J., Sharp P. A., Wahli W. W., Keller M. J. A high-efficiency HeLa cell nuclear transcription extract. DNA. 1988 Jan-Feb;7(1):47–55. doi: 10.1089/dna.1988.7.47. [DOI] [PubMed] [Google Scholar]
  30. Siebenlist U., Gilbert W. Contacts between Escherichia coli RNA polymerase and an early promoter of phage T7. Proc Natl Acad Sci U S A. 1980 Jan;77(1):122–126. doi: 10.1073/pnas.77.1.122. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Singh H., Sen R., Baltimore D., Sharp P. A. A nuclear factor that binds to a conserved sequence motif in transcriptional control elements of immunoglobulin genes. Nature. 1986 Jan 9;319(6049):154–158. doi: 10.1038/319154a0. [DOI] [PubMed] [Google Scholar]
  32. Wellman S. E., Casano P. J., Pilch D. R., Marzluff W. F., Sittman D. B. Characterization of mouse H3.3-like histone genes. Gene. 1987;59(1):29–39. doi: 10.1016/0378-1119(87)90263-0. [DOI] [PubMed] [Google Scholar]
  33. Wells D., Kedes L. Structure of a human histone cDNA: evidence that basally expressed histone genes have intervening sequences and encode polyadenylylated mRNAs. Proc Natl Acad Sci U S A. 1985 May;82(9):2834–2838. doi: 10.1073/pnas.82.9.2834. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Wu R. S., Bonner W. M. Separation of basal histone synthesis from S-phase histone synthesis in dividing cells. Cell. 1981 Dec;27(2 Pt 1):321–330. doi: 10.1016/0092-8674(81)90415-3. [DOI] [PubMed] [Google Scholar]
  35. Zambetti G., Stein J., Stein G. Role of messenger RNA subcellular localization in the posttranscriptional regulation of human histone gene expression. J Cell Physiol. 1990 Jul;144(1):175–182. doi: 10.1002/jcp.1041440123. [DOI] [PubMed] [Google Scholar]
  36. el-Hodiri H. M., Perry M. Interaction of the CCAAT displacement protein with shared regulatory elements required for transcription of paired histone genes. Mol Cell Biol. 1995 Jul;15(7):3587–3596. doi: 10.1128/mcb.15.7.3587. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. van Wijnen A. J., Aziz F., Graña X., De Luca A., Desai R. K., Jaarsveld K., Last T. J., Soprano K., Giordano A., Lian J. B. 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):12882–12886. doi: 10.1073/pnas.91.26.12882. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. van den Ent F. M., van Wijnen A. J., Lian J. B., Stein J. L., Stein G. S. 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):515–530. doi: 10.1002/jcp.1041590316. [DOI] [PubMed] [Google Scholar]

Articles from Nucleic Acids Research are provided here courtesy of Oxford University Press

RESOURCES