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Reduced levels of histone H3 acetylation on the inactive X chromosome in human females

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Abstract

Novel antibodies were generated that are highly selective for either acetylated or unacetylated iso-forms of histone H3, or the acetylated form of histone H4 in organisms as diverse asTetrahymena and humans. Using these antibodies as pair-wise sets in immunocytological analyses, we demonstrate that the inactive X chromosome is hypoacetylated for both histone H3 and H4 in female mammalian cells, whereas the antibody that recognizes the unacetylated form of histone H3 identifies all chromosomes uniformly. These data verify and extend previous results and suggest that hypoacetylation of core histones may be a general feature of the chromatin along the inactive X chromosome.

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References

  • Barr ML, Bertram EG (1949) A morphological distinction between neurones of the male and female and the behavior of the nucleolar satellite during accelerated nucleoprotein synthesis. Nature 163:676–677

    PubMed  CAS  Google Scholar 

  • Bauer WR, Hayes JJ, White JH, Wolffe AP (1994) Nucleosome structural changes due to acetylation. J. Mol Biol. 236:685–690

    Article  PubMed  CAS  Google Scholar 

  • Belyaev ND, Keohane AM, Turner BM (1996) Differential underacetylation of histones H2A, H3 and H4 on the inactive X chromosome in human female cells. Hum Genet. 97:573–578

    PubMed  CAS  Google Scholar 

  • Bickmore WA, Carothers AD (1995) Factors affecting the timing and imprinting of replication on a mammalian chromosome. J Cell Sci 108:2801–2809

    PubMed  CAS  Google Scholar 

  • Braunstein M, Rose AB, Holmes SG, Allis CD, Broach JR (1993) Transcriptional silencing in yeast is associated with reduced nucleosome acetylation. Genes Dev 7:592–604

    PubMed  CAS  Google Scholar 

  • Braunstein M, Sobel RE, Allis CD, Turner BM, Broach JR (1996) Efficient transcriptional silencing inSachcaromyces cerevisiae requires a heterochromatin histone acetylation pattern. Mol Cell Biol 16:4349–4356

    PubMed  CAS  Google Scholar 

  • Brownell JE, Zhou J, Ranalli T, Kobayashi R, Edmondson DG, Roth SY, Allis CD (1996) Tetrahymena histone acetyltransferase A: a homolog to yeast Gcn5p linking histone acetylation to gene activation. Cell 84:843–851

    Article  PubMed  CAS  Google Scholar 

  • Clayton A, Hebbes TR, Thorne AW, Crane-Robinson C (1993) Histone acetylation and gene induction in human cells. FEBS Lett 336:23–26

    Article  PubMed  CAS  Google Scholar 

  • Clemson CM, McNeil JA, Willard HF, Lawrence JB (1996) XIST RNA paints the inactive X chromosome at interphase: evidence for a novel RNA involved in nuclear chromosome structure. J Cell Biol 132:259–275

    Article  PubMed  CAS  Google Scholar 

  • Felsenfeld G (1992) Chromatin as an essential part of the transcriptional mechanism. Nature 355:219–224

    Article  PubMed  CAS  Google Scholar 

  • Gross DS, Garrard WT (1987) Poising chromatin for transcription. Trends Biochem Sci 12:293–297

    Article  CAS  Google Scholar 

  • Grunstein M (1990) Histone function in transcription. Annu Rev Cell Biol 6:643–648

    Article  PubMed  CAS  Google Scholar 

  • Hebbes TR, Thorne AW, Crane-Robinson C (1988) A direct link between core histone acetylation and transcriptionally active chromatin. EMBO J 7:1395–1402

    PubMed  CAS  Google Scholar 

  • Hebbes TR, Clayton AL, Thorne AW, Crane-Robinson C (1994) Core histone hyperacetylation co-maps with generalized DNase I sensitivity in the chicken β-globin chromosomal domain. EMBO J 13:1823–1830

    PubMed  CAS  Google Scholar 

  • Jeppesen P, Turner BM (1993) The inactive X chromosome in female mammals is distinguished by a lack of histone H4 acetylation, a cytogenetic marker for gene expression. Cell 74:281–189

    Article  PubMed  CAS  Google Scholar 

  • Johnson LM, Kayne PS, Kahn ES, Grunstein M (1990) Genetic evidence for an interaction between SIR3 and histone H4 in the repression of the silent mating loci inSaccharomyces cerevisiae. Proc Natl Acad Sci USA 87:6286–6290

    Article  PubMed  CAS  Google Scholar 

  • Kaslow DC, Migeon BR (1987) DNA methylation stabilizes X chromosome inactivation in eutherians but not in marsupials: evidence for multistep maintenance of mammalian X dosage compensation. Proc Natl Acad Sci USA 84:6210–6214

    Article  PubMed  CAS  Google Scholar 

  • Kayne PS, Kim UJ, Han M, Mullen JR, Yoshizaki F, Grunstein M (1988) Extremely conserved histone H4 terminus is dispensible for growth but essential for repressing the silent mating loci in yeast. Cell 55:27–39

    Article  PubMed  CAS  Google Scholar 

  • Kuo M-H, Brownell JE, Sobel RE, Ranalli TA, Cook RG, Edmondson DG, Roth SY, Allis CD (1996) Transcription-associated acetylation of histones H3 and H4 at specific lysines by Gen5p. Nature 383:269–272

    Article  PubMed  CAS  Google Scholar 

  • Lin R, Leone JW, Cook RG, Allis CD (1989) Antibodies specific to acetylated histones document the existence of deposition-and transcription-related histone acetylation inTetrahymena J Cell Biol 108:1577–1588

    Article  PubMed  CAS  Google Scholar 

  • Lock LF, Takagi N, Martin GR (1987) Methylation of the HPRT gene on the inactive X occurs after chromosome inactivation. Cell 8:39–46

    Article  Google Scholar 

  • Lyon MF (1961) Gene action in the X-chromosome of the mouse (Mus musculus L.). Nature 190:372–373

    Article  PubMed  CAS  Google Scholar 

  • Megee PC, Morgan BA, Mittman BA, Mitchell-Smith M (1990) Genetic analysis of histone H4: essential role of lysines subject to reversible acetylation. Science 247:841–845

    Article  PubMed  CAS  Google Scholar 

  • Morishima A, Grumbach MM, Taylor JH (1962) Asynchronous duplication of human chromosomes and the origin of sex chromatin. Proc Natl Acad Sci USA 48:756–763

    Article  PubMed  CAS  Google Scholar 

  • Norton VG, Marvin KW, Yau P, Bradbury EM (1990) Nucleosome linking number change controlled by acetylation of histones H3 and H4. J Biol Chem 265:19848–19852

    PubMed  CAS  Google Scholar 

  • O'Neil LP, Turner BM (1996) Histone H4 acetylation distinguishes coding regions of the human genome from heterochromatin in a differentiation-dependent but transcription-independent manner. EMBO J 14:3946–3957

    Google Scholar 

  • Owen-Hughes TA, Workman JL (1994) Experimental analysis of chromatin function in transcription control. Crit Rev Eukaryot Gene Expr 4:403–441

    PubMed  CAS  Google Scholar 

  • Park EC, Szostak JW (1990) Point mutations in the yeast histone H4 gene prevent silencing of the silent mating locus HML. Mol Cell Biol 10:4932–4934

    PubMed  CAS  Google Scholar 

  • Roth S, Allis CD (1992) Chromatin condensation: does histone H1 dephosphorylation play a role? Trends Biochem Sci 17:93–98

    Article  PubMed  CAS  Google Scholar 

  • Sobel RE, Cook RG, Perry CA, Annunziato AT, Allis CD (1995) Conservation of deposition related acetylation sites in newly synthesized histones H3 and H4. Proc Natl Acad Sci USA 92:1237–1241

    Article  PubMed  CAS  Google Scholar 

  • Stargell LA, Bowen J, Dadd CA, Dedon PC, Davis M, Cook RG, Allis CD, Gorovsky MA (1993) Temporal and spatial association of histone H2A variant hv1 with transcriptionally competent chromatin during nuclear development inTetrahymena thermophila. Genes Dev 7:2641–2651

    PubMed  CAS  Google Scholar 

  • Taunton J, Hassig CA, Schreiber SL (1996) A mammalian histone deacetylase related to the yeast transcriptional regulator Rpd3p. Science 272:408–411

    Article  PubMed  CAS  Google Scholar 

  • Taylor JH (1960) Asynchronous duplication of chromosomes in cultured cells of Chinese hamster. J Biophys Biochem Cytol 7:455–464

    Article  PubMed  CAS  Google Scholar 

  • Turner BM, O'Neil LP (1995) Histone acetylation in chromatin and chromosomes. Semin Cell Biol 6:229–236

    Article  PubMed  CAS  Google Scholar 

  • Turner BM, Birley AJ, Lavender J (1992) Histone H4 isoforms acetylated at specific lysine residues define individual chromosomes and chromatin domains inDrosophila polytene nuclei. Cell 69:375–384

    Article  PubMed  CAS  Google Scholar 

  • Van Holde KE (1989) Chromatin, Springer-Verlag, New York

    Google Scholar 

  • Vettese-Dadey M, Grant PA, Hebbes TR, Crane-Robinson C, Allis CD, Workman JL (1996) Acetylation of histone H4 plays a primary role in enhancing transcription factor binding to nucleosomal DNA. EMBO J 15:2508–2518

    PubMed  CAS  Google Scholar 

  • Viegas-Pequignot E, Dutrillaux B, Thomas G (1988) Inactive X chromosome has the highest concentration of unmethylatedHha I sites. Proc Natl Acad Sci USA 85:7657–7660

    Article  PubMed  CAS  Google Scholar 

  • Wolffe AP (1994) Nucleosomal positioning and modification: chromatin structures that potentiate transcription. Trends Biochem Sci 19:240–244

    Article  PubMed  CAS  Google Scholar 

  • Wolffe AP (1995) Chromatin structure and function. Academic Press, London

    Google Scholar 

  • Wolffe AP (1996) Histone deacetylase: a regulator of transcription. Science 272:371–372

    Article  PubMed  CAS  Google Scholar 

  • Wolffe AP, Pruss D (1996a) Targeting chromating disruption: transcription regulators that acetylate histones. Cell 84:817–819

    Article  PubMed  CAS  Google Scholar 

  • Wolffe AP, Pruss D (1996b) Deviant nucleosomes: the functional specialization of chromatin. Trends Genet 12:58–62

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Molecular and Human Genetics, Baylor College of Medicine, 77030, Houston, TX, USA

    Barbara A. Boggs & A. Craig Chinault

  2. Department of Biology, University of Rochester, 14627, Rochester, NY, USA

    Bernadette Connors, Richard E. Sobel & C. David Allis

Authors
  1. Barbara A. Boggs
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  2. Bernadette Connors
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  3. Richard E. Sobel
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  4. A. Craig Chinault
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  5. C. David Allis
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Corresponding author

Correspondence to C. David Allis.

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Edited by: D. Bazett-Jones

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Boggs, B.A., Connors, B., Sobel, R.E. et al. Reduced levels of histone H3 acetylation on the inactive X chromosome in human females. Chromosoma 105, 303–309 (1996). https://doi.org/10.1007/BF02524648

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  • DOI: https://doi.org/10.1007/BF02524648

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