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PMID: 10570157 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Promoter-specific hypoacetylation of X-inactivated genes.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 96 ·No. 24 ·1999-11-23 ·Pages 13825-30

Gilbert SL, Sharp PA

Abstract

The histone H4 acetylation status of the active X (Xa) and inactive X (Xi) chromosomes was investigated at the level of individual genes. A moderate level of acetylation was observed along the lengths of genes on both the Xi and Xa, regardless of their X inactivation status. However, this moderate level of acetylation was modified specifically in promoter regions. Transcriptionally active genes showed elevated levels of acetylation at their promoters on both the Xi and Xa. In contrast, promoters of X-inactivated genes were markedly hypoacetylated, which coincided with the methylation of adjacent CG dinucleotides. This promoter-specific hypoacetylation may be a key component of an X inactivation machinery that operates at the level of individual genes.

MeSH Terms
Acetylation Animals Cell Line Cricetinae DNA Methylation Dosage Compensation, Genetic Female Histones/metabolism Humans Lysine/metabolism Male Promoter Regions, Genetic Transcription, Genetic X Chromosome
Chemicals
Histones Lysine
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Gilbert S L
Department of Biology, Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Sharp P A
References (43)
43 references, click to expand
  1. The murine Xe169 gene escapes X-inactivation like its human homologue.
    Nat Genet. 1994 Aug;7(4):491-6 PMID: 7951318
  2. A novel X gene with a widely transcribed Y-linked homologue escapes X-inactivation in mouse and human.
    Hum Mol Genet. 1994 Jun;3(6):879-84 PMID: 7951230
  3. Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription.
    Nat Genet. 1998 Jun;19(2):187-91 PMID: 9620779
  4. Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex.
    Nature. 1998 May 28;393(6683):386-9 PMID: 9620804
  5. Histone macroH2A1 is concentrated in the inactive X chromosome of female mammals.
    Nature. 1998 Jun 11;393(6685):599-601 PMID: 9634239
  6. A proposed path by which genes common to mammalian X and Y chromosomes evolve to become X inactivated.
    Nature. 1998 Aug 20;394(6695):776-80 PMID: 9723615
  7. A developmental switch in H4 acetylation upstream of Xist plays a role in X chromosome inactivation.
    EMBO J. 1999 May 17;18(10):2897-907 PMID: 10329635
  8. Chromatin structure analysis of the mouse Xist locus.
    Proc Natl Acad Sci U S A. 1999 Jun 22;96(13):7155-60 PMID: 10377384
  9. Requirement for Xist in X chromosome inactivation.
    Nature. 1996 Jan 11;379(6561):131-7 PMID: 8538762
  10. Differential underacetylation of histones H2A, H3 and H4 on the inactive X chromosome in human female cells.
    Hum Genet. 1996 May;97(5):573-8 PMID: 8655133
  11. A 450 kb transgene displays properties of the mammalian X-inactivation center.
    Cell. 1996 Jul 12;86(1):83-94 PMID: 8689690
  12. Role of late replication timing in the silencing of X-linked genes.
    Hum Mol Genet. 1996 Sep;5(9):1345-53 PMID: 8872476
  13. Reduced levels of histone H3 acetylation on the inactive X chromosome in human females.
    Chromosoma. 1996 Dec;105(5):303-9 PMID: 8939823
  14. X-Inactivation and histone H4 acetylation in embryonic stem cells.
    Dev Biol. 1996 Dec 15;180(2):618-30 PMID: 8954732
  15. The TAF(II)250 subunit of TFIID has histone acetyltransferase activity.
    Cell. 1996 Dec 27;87(7):1261-70 PMID: 8980232
  16. Xist-deficient mice are defective in dosage compensation but not spermatogenesis.
    Genes Dev. 1997 Jan 15;11(2):156-66 PMID: 9009199
  17. Long-range cis effects of ectopic X-inactivation centres on a mouse autosome.
    Nature. 1997 Mar 20;386(6622):275-9 PMID: 9069285
  18. The great escape.
    Am J Hum Genet. 1997 Jun;60(6):1312-5 PMID: 9199551
  19. Expression of genes from the human active and inactive X chromosomes.
    Am J Hum Genet. 1997 Jun;60(6):1333-43 PMID: 9199554
  20. X chromosome inactivation is mediated by Xist RNA stabilization.
    Cell. 1997 Sep 5;90(5):907-16 PMID: 9298902
  21. Activation of SRF-regulated chromosomal templates by Rho-family GTPases requires a signal that also induces H4 hyperacetylation.
    Cell. 1998 Feb 20;92(4):475-87 PMID: 9491889
  22. Histone acetyltransferase activity of yeast Gcn5p is required for the activation of target genes in vivo.
    Genes Dev. 1998 Mar 1;12(5):627-39 PMID: 9499399
  23. Reactivation of XIST in normal fibroblasts and a somatic cell hybrid: abnormal localization of XIST RNA in hybrid cells.
    Proc Natl Acad Sci U S A. 1998 Apr 28;95(9):5133-8 PMID: 9560241
  24. Transcriptional repression by UME6 involves deacetylation of lysine 5 of histone H4 by RPD3.
    Nature. 1998 Apr 23;392(6678):831-5 PMID: 9572144
  25. X inactivation, differentiation, and DNA methylation.
    Cytogenet Cell Genet. 1975;14(1):9-25 PMID: 1093816
  26. Reactivation of an inactive human X chromosome: evidence for X inactivation by DNA methylation.
    Science. 1981 Jan 23;211(4480):393-6 PMID: 6164095
  27. Extent of histone modifications and H1(0) content during cell cycle progression in the presence of butyrate.
    Exp Cell Res. 1983 Sep;147(2):407-17 PMID: 6617774
  28. Absence of methylation of a CpG-rich region at the 5' end of the MIC2 gene on the active X, the inactive X, and the Y chromosome.
    Proc Natl Acad Sci U S A. 1988 Aug;85(15):5605-9 PMID: 2456574
  29. Demethylation of specific sites in the 5' region of the inactive X-linked human phosphoglycerate kinase gene correlates with the appearance of nuclease sensitivity and gene expression.
    Mol Cell Biol. 1988 Nov;8(11):4692-9 PMID: 2850467
  30. Specific antibodies reveal ordered and cell-cycle-related use of histone-H4 acetylation sites in mammalian cells.
    Eur J Biochem. 1989 Jan 15;179(1):131-9 PMID: 2917555
  31. Antibodies specific to acetylated histones document the existence of deposition- and transcription-related histone acetylation in Tetrahymena.
    J Cell Biol. 1989 May;108(5):1577-88 PMID: 2654136
  32. ZFX has a gene structure similar to ZFY, the putative human sex determinant, and escapes X inactivation.
    Cell. 1989 Jun 30;57(7):1247-58 PMID: 2500252
  33. Asynchronous replication of homologous loci on human active and inactive X chromosomes.
    Proc Natl Acad Sci U S A. 1990 May;87(10):3685-9 PMID: 2339112
  34. 5-Azacytidine-induced reactivation of the human X chromosome-linked PGK1 gene is associated with a large region of cytosine demethylation in the 5' CpG island.
    Proc Natl Acad Sci U S A. 1990 Jun;87(11):4174-8 PMID: 1693431
  35. A gene from the region of the human X inactivation centre is expressed exclusively from the inactive X chromosome.
    Nature. 1991 Jan 3;349(6304):38-44 PMID: 1985261
  36. Methylation and sequence analysis around EagI sites: identification of 28 new CpG islands in XQ24-XQ28.
    Nucleic Acids Res. 1992 Feb 25;20(4):727-33 PMID: 1542569
  37. Methylation status of CpG-rich islands on active and inactive mouse X chromosomes.
    Mamm Genome. 1991;1(2):78-83 PMID: 1799791
  38. The human XIST gene: analysis of a 17 kb inactive X-specific RNA that contains conserved repeats and is highly localized within the nucleus.
    Cell. 1992 Oct 30;71(3):527-42 PMID: 1423611
  39. Transcriptional silencing in yeast is associated with reduced nucleosome acetylation.
    Genes Dev. 1993 Apr;7(4):592-604 PMID: 8458576
  40. The inactive X chromosome in female mammals is distinguished by a lack of histone H4 acetylation, a cytogenetic marker for gene expression.
    Cell. 1993 Jul 30;74(2):281-9 PMID: 8343956
  41. Evolutionary conservation of possible functional domains of the human and murine XIST genes.
    Hum Mol Genet. 1993 Jun;2(6):663-72 PMID: 8353487
  42. High-resolution methylation analysis of the human hypoxanthine phosphoribosyltransferase gene 5' region on the active and inactive X chromosomes: correlation with binding sites for transcription factors.
    Mol Cell Biol. 1994 Feb;14(2):1419-30 PMID: 8289817
  43. Loss of methylation activates Xist in somatic but not in embryonic cells.
    Genes Dev. 1995 Oct 1;9(19):2325-34 PMID: 7557385
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.96.24.13825
Published
1999-11-23
Pages
13825-30
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC24149
Subset
IM
Grants
NCI NIH HHS · P01 CA042063 · United States
NCI NIH HHS · P30 CA014051 · United States
NCI NIH HHS · P30-CA14051 · United States
NIAID NIH HHS · R01-AI32486 · United States
NCI NIH HHS · P01-CA42063 · United States
External Links
PubMed source DOI: 10.1073/pnas.96.24.13825 PMC Full Text View journal details
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