Spread of X-chromosome inactivation into autosomal sequences: role for DNA elements, chromatin features and chromosomal domains.
Spread of X-chromosome inactivation into autosomal sequences: role for DNA elements, chromatin features and chromosomal domains.
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DOI：
10.1093/hmg/ddt513
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发表时间：
2014-03-01
影响因子：
3.5
通讯作者：
Brown CJ
中科院分区：
文献类型：
--
作者：
Cotton AM;Chen CY;Lam LL;Wasserman WW;Kobor MS;Brown CJ
X染色体失活导致男性和女性X染色体之间的剂量相等;然而，超过15%的人类X连锁基因逃脱沉默，这些基因富集在X染色体进化上更年轻的短臂上。失活扩散到易位的常染色体物质上，使得研究失活时不需要混淆X染色体的进化史。常染色体上沉默的异质性和降低的程度是沉默传播背后的DNA元件的重要性的证据。我们使用Illumina Infinium HumanMethylation 450阵列评估了六种不平衡X-常染色体易位中的DNA甲基化。2 - 42%的易位的常染色体基因显示出这种沉默标记，在三体常染色体区域观察到最高程度的失活。通常，沉默的程度最大接近易位断裂点;然而，在远超过100 kb的常染色体DNA中检测到沉默。发现Alu元件富集在从失活中逃脱的常染色体基因处，而L1 s富集在受试者基因处。在没有易位的细胞中，那些在易位时变得沉默的基因富集了异染色质特征，例如EZH 2和H3 K27 me 3，这表明潜在的染色质结构使基因倾向于沉默。此外，拓扑结构域的分析表明，常见的失活状态的常染色体基因的物理聚类。总的来说，我们的分析表明，DNA序列，染色质特征和染色体的三维结构之间存在复杂的相互作用。
X-chromosome inactivation results in dosage equivalence between the X chromosome in males and females; however, over 15% of human X-linked genes escape silencing and these genes are enriched on the evolutionarily younger short arm of the X chromosome. The spread of inactivation onto translocated autosomal material allows the study of inactivation without the confounding evolutionary history of the X chromosome. The heterogeneity and reduced extent of silencing on autosomes are evidence for the importance of DNA elements underlying the spread of silencing. We have assessed DNA methylation in six unbalanced X-autosome translocations using the Illumina Infinium HumanMethylation450 array. Two to 42% of translocated autosomal genes showed this mark of silencing, with the highest degree of inactivation observed for trisomic autosomal regions. Generally, the extent of silencing was greatest close to the translocation breakpoint; however, silencing was detected well over 100 kb into the autosomal DNA. Alu elements were found to be enriched at autosomal genes that escaped from inactivation while L1s were enriched at subject genes. In cells without the translocation, there was enrichment of heterochromatic features such as EZH2 and H3K27me3 for those genes that become silenced when translocated, suggesting that underlying chromatin structure predisposes genes towards silencing. Additionally, the analysis of topological domains indicated physical clustering of autosomal genes of common inactivation status. Overall, our analysis indicated a complex interaction between DNA sequence, chromatin features and the three-dimensional structure of the chromosome.
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影响因子：
14.9
作者：
Almeida LG;Sakabe NJ;deOliveira AR;Silva MC;Mundstein AS;Cohen T;Chen YT;Chua R;Gurung S;Gnjatic S;Jungbluth AA;Caballero OL;Bairoch A;Kiesler E;White SL;Simpson AJ;Old LJ;Camargo AA;Vasconcelos AT
通讯作者：
Vasconcelos AT
影响因子：
3.5
作者：
Hall, LL;Clemson, CM;Lawrence, JB
通讯作者：
Lawrence, JB
DOI：
10.1073/pnas.0603754103
发表时间：
2006-06-27
影响因子：
11.1
作者：
Ciavatta, Dominic;Kalantry, Sundeep;Smithies, Oliver
通讯作者：
Smithies, Oliver
影响因子：
5.2
作者：
Giorda, Roberto;Bonaglia, M. Clara;Zuffardi, Orsetta
通讯作者：
Zuffardi, Orsetta
影响因子：
5.3
作者：
DISTECHE, CM;SWISSHELM, K;PAGON, RA
通讯作者：
PAGON, RA