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 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.
Matarazzo
Maria Rosaria
MR
Institute of Genetics and Biophysics 'A Buzzati Traverso', CNR, Naples, Italy.
De Bonis
Maria Luigia
ML
Gregory
Richard I
RI
Vacca
Marcella
M
Hansen
R Scott
RS
Mercadante
Grazia
G
D'Urso
Michele
M
Feil
Robert
R
D'Esposito
Maurizio
M
D000483:Alleles; D002461:Cell Line, Transformed; D002843:Chromatin / Q000235:genetics; D041321:Chromosomes, Human, X / Q000235:genetics*; D041322:Chromosomes, Human, Y / Q000235:genetics*; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D005260:Female; D005347:Fibroblasts / Q000737:chemistry / Q000378:metabolism / Q000821:virology; D005786:Gene Expression Regulation / Q000235:genetics; D020868:Gene Silencing; D006580:Genetic Carrier Screening; D004854:Herpesvirus 4, Human; D006657:Histones / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D006822:Hybrid Cells; D008214:Lymphocytes / Q000737:chemistry / Q000378:metabolism / Q000821:virology; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D050683:R-SNARE Proteins
D002843:Chromatin; D006657:Histones; D008565:Membrane Proteins; D050683:R-SNARE Proteins; C121241:VAMP7 protein, human