Search tips
Search criteria 


Logo of molcellbPermissionsJournals.ASM.orgJournalMCB ArticleJournal InfoAuthorsReviewers
Mol Cell Biol. 1992 December; 12(12): 5455–5463.
PMCID: PMC360483

Histone H3 transcription in Saccharomyces cerevisiae is controlled by multiple cell cycle activation sites and a constitutive negative regulatory element.


The promoters of the Saccharomyces cerevisiae histone H3 and H4 genes were examined for cis-acting DNA sequence elements regulating transcription and cell division cycle control. Deletion and linker disruption mutations identified two classes of regulatory elements: multiple cell cycle activation (CCA) sites and a negative regulatory site (NRS). Duplicate 19-bp CCA sites are present in both the copy I and copy II histone H3-H4 promoters arranged as inverted repeats separated by 45 and 68 bp. The CCA sites are both necessary and sufficient to activate transcription under cell division cycle control. A single CCA site provides cell cycle control but is a weak transcriptional activator, while an inverted repeat comprising two CCA sites provides both strong transcriptional activation and cell division cycle control. The NRS was identified in the copy I histone H3-H4 promoter. Deletion or disruption of the NRS increased the level of the histone H3 promoter activity but did not alter the cell division cycle periodicity of transcription. When the CCA sites were deleted from the histone promoter, the NRS element was unable to confer cell division cycle control on the remaining basal level of transcription. When the NRS element was inserted into the promoter of a foreign reporter gene, transcription was constitutively repressed and did not acquire cell cycle regulation.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (2.2M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Andrews BJ, Herskowitz I. The yeast SWI4 protein contains a motif present in developmental regulators and is part of a complex involved in cell-cycle-dependent transcription. Nature. 1989 Dec 14;342(6251):830–833. [PubMed]
  • Andrews BJ, Herskowitz I. Regulation of cell cycle-dependent gene expression in yeast. J Biol Chem. 1990 Aug 25;265(24):14057–14060. [PubMed]
  • Breeden L, Mikesell GE. Cell cycle-specific expression of the SWI4 transcription factor is required for the cell cycle regulation of HO transcription. Genes Dev. 1991 Jul;5(7):1183–1190. [PubMed]
  • Breeden L, Nasmyth K. Cell cycle control of the yeast HO gene: cis- and trans-acting regulators. Cell. 1987 Feb 13;48(3):389–397. [PubMed]
  • Casadaban MJ, Chou J, Cohen SN. In vitro gene fusions that join an enzymatically active beta-galactosidase segment to amino-terminal fragments of exogenous proteins: Escherichia coli plasmid vectors for the detection and cloning of translational initiation signals. J Bacteriol. 1980 Aug;143(2):971–980. [PMC free article] [PubMed]
  • Cross SL, Smith MM. Comparison of the structure and cell cycle expression of mRNAs encoded by two histone H3-H4 loci in Saccharomyces cerevisiae. Mol Cell Biol. 1988 Feb;8(2):945–954. [PMC free article] [PubMed]
  • Dailey L, Hanly SM, Roeder RG, Heintz N. Distinct transcription factors bind specifically to two regions of the human histone H4 promoter. Proc Natl Acad Sci U S A. 1986 Oct;83(19):7241–7245. [PubMed]
  • Dalton S, Wells JR. Maximal binding levels of an H1 histone gene-specific factor in S-phase correlate with maximal H1 gene transcription. Mol Cell Biol. 1988 Oct;8(10):4576–4578. [PMC free article] [PubMed]
  • Drebot MA, Veinot-Drebot LM, Singer RA, Johnston GC. Induction of yeast histone genes by stimulation of stationary-phase cells. Mol Cell Biol. 1990 Dec;10(12):6356–6361. [PMC free article] [PubMed]
  • Elledge SJ, Davis RW. Two genes differentially regulated in the cell cycle and by DNA-damaging agents encode alternative regulatory subunits of ribonucleotide reductase. Genes Dev. 1990 May;4(5):740–751. [PubMed]
  • Gallinari P, La Bella F, Heintz N. Characterization and purification of H1TF2, a novel CCAAT-binding protein that interacts with a histone H1 subtype-specific consensus element. Mol Cell Biol. 1989 Apr;9(4):1566–1575. [PMC free article] [PubMed]
  • Goad WB, Kanehisa MI. Pattern recognition in nucleic acid sequences. I. A general method for finding local homologies and symmetries. Nucleic Acids Res. 1982 Jan 11;10(1):247–263. [PMC free article] [PubMed]
  • Gordon CB, Campbell JL. A cell cycle-responsive transcriptional control element and a negative control element in the gene encoding DNA polymerase alpha in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):6058–6062. [PubMed]
  • Gordon CN, Elliott SC. Fractionation of Saccharomyces cerevisiae cell populations by centrifugal elutriation. J Bacteriol. 1977 Jan;129(1):97–100. [PMC free article] [PubMed]
  • Guarente L. Yeast promoters and lacZ fusions designed to study expression of cloned genes in yeast. Methods Enzymol. 1983;101:181–191. [PubMed]
  • Guarente L, Ptashne M. Fusion of Escherichia coli lacZ to the cytochrome c gene of Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 1981 Apr;78(4):2199–2203. [PubMed]
  • Hartwell LH, Weinert TA. Checkpoints: controls that ensure the order of cell cycle events. Science. 1989 Nov 3;246(4930):629–634. [PubMed]
  • Heintz N. The regulation of histone gene expression during the cell cycle. Biochim Biophys Acta. 1991 Mar 26;1088(3):327–339. [PubMed]
  • Hereford L, Bromley S, Osley MA. Periodic transcription of yeast histone genes. Cell. 1982 Aug;30(1):305–310. [PubMed]
  • Hereford LM, Osley MA, Ludwig TR, 2nd, McLaughlin CS. Cell-cycle regulation of yeast histone mRNA. Cell. 1981 May;24(2):367–375. [PubMed]
  • Kupiec M, Simchen G. Regulation of the RAD6 gene of Saccharomyces cerevisiae in the mitotic cell cycle and in meiosis. Mol Gen Genet. 1986 Jun;203(3):538–543. [PubMed]
  • LaBella F, Sive HL, Roeder RG, Heintz N. Cell-cycle regulation of a human histone H2b gene is mediated by the H2b subtype-specific consensus element. Genes Dev. 1988 Jan;2(1):32–39. [PubMed]
  • Lörincz AT, Miller MJ, Xuong NH, Geiduschek EP. Identification of proteins whose synthesis is modulated during the cell cycle of Saccharomyces cerevisiae. Mol Cell Biol. 1982 Dec;2(12):1532–1549. [PMC free article] [PubMed]
  • Lowndes NF, Johnson AL, Johnston LH. Coordination of expression of DNA synthesis genes in budding yeast by a cell-cycle regulated trans factor. Nature. 1991 Mar 21;350(6315):247–250. [PubMed]
  • Lycan DE, Osley MA, Hereford LM. Role of transcriptional and posttranscriptional regulation in expression of histone genes in Saccharomyces cerevisiae. Mol Cell Biol. 1987 Feb;7(2):614–621. [PMC free article] [PubMed]
  • McIntosh EM, Atkinson T, Storms RK, Smith M. Characterization of a short, cis-acting DNA sequence which conveys cell cycle stage-dependent transcription in Saccharomyces cerevisiae. Mol Cell Biol. 1991 Jan;11(1):329–337. [PMC free article] [PubMed]
  • Moran L, Norris D, Osley MA. A yeast H2A-H2B promoter can be regulated by changes in histone gene copy number. Genes Dev. 1990 May;4(5):752–763. [PubMed]
  • Nasmyth K. Molecular analysis of a cell lineage. Nature. 1983 Apr 21;302(5910):670–676. [PubMed]
  • Nasmyth K. At least 1400 base pairs of 5'-flanking DNA is required for the correct expression of the HO gene in yeast. Cell. 1985 Aug;42(1):213–223. [PubMed]
  • Nasmyth K, Seddon A, Ammerer G. Cell cycle regulation of SW15 is required for mother-cell-specific HO transcription in yeast. Cell. 1987 May 22;49(4):549–558. [PubMed]
  • Osley MA. The regulation of histone synthesis in the cell cycle. Annu Rev Biochem. 1991;60:827–861. [PubMed]
  • Osley MA, Gould J, Kim S, Kane MY, Hereford L. Identification of sequences in a yeast histone promoter involved in periodic transcription. Cell. 1986 May 23;45(4):537–544. [PubMed]
  • Osley MA, Lycan D. Trans-acting regulatory mutations that alter transcription of Saccharomyces cerevisiae histone genes. Mol Cell Biol. 1987 Dec;7(12):4204–4210. [PMC free article] [PubMed]
  • Rymond BC, Zitomer RS, Schümperli D, Rosenberg M. The expression in yeast of the Escherichia coli galK gene on CYC1::galK fusion plasmids. Gene. 1983 Nov;25(2-3):249–262. [PubMed]
  • Sanger F, Nicklen S, Coulson AR. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. [PubMed]
  • Sikorski RS, Hieter P. A system of shuttle vectors and yeast host strains designed for efficient manipulation of DNA in Saccharomyces cerevisiae. Genetics. 1989 May;122(1):19–27. [PubMed]
  • Smith MM. Molecular evolution of the Saccharomyces cerevisiae histone gene loci. J Mol Evol. 1987;24(3):252–259. [PubMed]
  • Smith MM. Mutations that affect chromosomal proteins in yeast. Methods Cell Biol. 1991;35:485–523. [PubMed]
  • Wu RS, Bonner WM. Separation of basal histone synthesis from S-phase histone synthesis in dividing cells. Cell. 1981 Dec;27(2 Pt 1):321–330. [PubMed]
  • Xu HX, Johnson L, Grunstein M. Coding and noncoding sequences at the 3' end of yeast histone H2B mRNA confer cell cycle regulation. Mol Cell Biol. 1990 Jun;10(6):2687–2694. [PMC free article] [PubMed]

Articles from Molecular and Cellular Biology are provided here courtesy of American Society for Microbiology (ASM)