Allelic inactivation of the pseudoautosomal gene SYBL1 is controlled by epigenetic mechanisms common to the X and Y chromosomes

On the human long-arm pseudoautosomal region (XqPAR), genes that are subject to inactivation are closely linked with those that escape. Genes subject to inactivation are not only silenced on the inactive X in females, but they are also inactivated on the Y chromosome in males. One of the genes subje...

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Veröffentlicht in:Human molecular genetics 2002-12, Vol.11 (25), p.3191-3198
Hauptverfasser: Matarazzo, Maria Rosaria, De Bonis, Maria Luigia, Gregory, Richard I., Vacca, Marcella, Hansen, R. Scott, Mercadante, Grazia, D'Urso, Michele, Feil, Robert, D'Esposito, Maurizio
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container_issue 25
container_start_page 3191
container_title Human molecular genetics
container_volume 11
creator Matarazzo, Maria Rosaria
De Bonis, Maria Luigia
Gregory, Richard I.
Vacca, Marcella
Hansen, R. Scott
Mercadante, Grazia
D'Urso, Michele
Feil, Robert
D'Esposito, Maurizio
description On the human long-arm pseudoautosomal region (XqPAR), genes that are subject to inactivation are closely linked with those that escape. Genes subject to inactivation are not only silenced on the inactive X in females, but they are also inactivated on the Y chromosome in males. One of the genes subject to this unusual inactivation pattern is the synaptobrevin-like 1 gene (SYBL1). Previously we showed that its silencing on the inactive X and the Y allele involves DNA methylation. This study explores the molecular events associated with SYBL1 silencing and investigates their relationship. Promoter DNA methylation profiles were determined by bisulfite sequencing and immunoprecipitation experiments demonstrate that chromatin on the repressed Xi and the Y alleles has underacetylated histones H3 and H4 and H3-lysine 9 methylation. In addition, the inactive X and the Y allele were found to have a condensed chromatin conformation. In contrast, the expressed allele shows H3 and H4 acetylation, H3-lysine 4 methylation and a less compacted chromatin conformation. In ICF syndrome, a human disease affecting DNA methylation, SYBL1 escapes from silencing and this correlates with altered patterns of histone methylation and acetylation. Combined, our data suggest that specific combinations of histone methylation and acetylation are involved in the somatic maintenance of permissive and repressed chromatin states at SYBL1. Although it is unclear at present how this allele-specific silencing comes about, the data also indicate that the epigenetic features of the ‘Y inactivation’ of SYBL1 are mechanistically similar to those associated with X-chromosome inactivation.
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Promoter DNA methylation profiles were determined by bisulfite sequencing and immunoprecipitation experiments demonstrate that chromatin on the repressed Xi and the Y alleles has underacetylated histones H3 and H4 and H3-lysine 9 methylation. In addition, the inactive X and the Y allele were found to have a condensed chromatin conformation. In contrast, the expressed allele shows H3 and H4 acetylation, H3-lysine 4 methylation and a less compacted chromatin conformation. In ICF syndrome, a human disease affecting DNA methylation, SYBL1 escapes from silencing and this correlates with altered patterns of histone methylation and acetylation. Combined, our data suggest that specific combinations of histone methylation and acetylation are involved in the somatic maintenance of permissive and repressed chromatin states at SYBL1. 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Scott</creatorcontrib><creatorcontrib>Mercadante, Grazia</creatorcontrib><creatorcontrib>D'Urso, Michele</creatorcontrib><creatorcontrib>Feil, Robert</creatorcontrib><creatorcontrib>D'Esposito, Maurizio</creatorcontrib><title>Allelic inactivation of the pseudoautosomal gene SYBL1 is controlled by epigenetic mechanisms common to the X and Y chromosomes</title><title>Human molecular genetics</title><addtitle>Hum. Mol. Genet</addtitle><description>On the human long-arm pseudoautosomal region (XqPAR), genes that are subject to inactivation are closely linked with those that escape. Genes subject to inactivation are not only silenced on the inactive X in females, but they are also inactivated on the Y chromosome in males. One of the genes subject to this unusual inactivation pattern is the synaptobrevin-like 1 gene (SYBL1). Previously we showed that its silencing on the inactive X and the Y allele involves DNA methylation. 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Combined, our data suggest that specific combinations of histone methylation and acetylation are involved in the somatic maintenance of permissive and repressed chromatin states at SYBL1. Although it is unclear at present how this allele-specific silencing comes about, the data also indicate that the epigenetic features of the ‘Y inactivation’ of SYBL1 are mechanistically similar to those associated with X-chromosome inactivation.</abstract><cop>Oxford</cop><pub>Oxford University Press</pub><pmid>12444103</pmid><doi>10.1093/hmg/11.25.3191</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0002-5671-5860</orcidid></addata></record>
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subjects Alleles
Biochemistry, Molecular Biology
Biological and medical sciences
Cell Line, Transformed
Chromatin - genetics
Chromosomes, Human, X - genetics
Chromosomes, Human, Y - genetics
CpG Islands - genetics
DNA Methylation
Female
Fibroblasts - chemistry
Fibroblasts - metabolism
Fibroblasts - virology
Fundamental and applied biological sciences. Psychology
Gene expression
Gene Expression Regulation - genetics
Gene Silencing
Genetic Carrier Screening
Herpesvirus 4, Human
Histones - chemistry
Histones - metabolism
Humans
Hybrid Cells
Life Sciences
Lymphocytes - chemistry
Lymphocytes - metabolism
Lymphocytes - virology
Male
Membrane Proteins - biosynthesis
Membrane Proteins - genetics
Molecular and cellular biology
Molecular genetics
Promoter Regions, Genetic - genetics
R-SNARE Proteins
title Allelic inactivation of the pseudoautosomal gene SYBL1 is controlled by epigenetic mechanisms common to the X and Y chromosomes
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