Allelic inactivation of the pseudoautosomal gene SYBL1 is controlled by epigenetic mechanisms common to the X and Y chromosomes
Allelic inactivation of the pseudoautosomal gene SYBL1 is controlled by epigenetic mechanisms common to the X and Y chromosomes
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DOI：
10.1093/hmg/11.25.3191
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发表时间：
2002-12-01
影响因子：
3.5
通讯作者：
D'Esposito, M
中科院分区：
文献类型：
--
作者：
Matarazzo, MR;De Bonis, ML;D'Esposito, M
在人类长臂伪常染色体区域(XqPAR)上，容易失活的基因与逃脱的基因密切相关。失活的基因不仅在女性的X染色体上失活，而且在男性的Y染色体上也失活。受到这种不同寻常的失活模式影响的基因之一是突触素样蛋白1基因(SYBL1)。在此之前，我们已经证明它对不活跃的X和Y等位基因的沉默涉及DNA甲基化。本研究探讨了与SYBL1沉默相关的分子事件及其相互关系。亚硫酸氢盐测序和免疫沉淀实验表明，被抑制的XI和Y等位基因上的染色质使组蛋白H3、H4和H3-赖氨酸9发生了低乙酰化。此外，不活跃的X等位基因和Y等位基因具有浓缩的染色质构象。相反，表达的等位基因显示H3和H4乙酰化，H3-赖氨酸4甲基化和较不紧密的染色质构象。在ICF综合征，一种影响DNA甲基化的人类疾病，SYBL1逃脱沉默，这与组蛋白甲基化和乙酰化的改变模式相关。综上所述，我们的数据表明，组蛋白甲基化和乙酰化的特定组合参与了SYBL1染色质允许状态和抑制状态的体细胞维持。虽然目前尚不清楚这种等位基因特异性沉默是如何产生的，但数据也表明，SYBL1的Y失活的表观遗传学特征在机制上类似于与X染色体失活相关的特征。
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.