The macrosatellite DXZ4 mediates CTCF-dependent long-range intrachromosomal interactions on the human inactive X chromosome
The macrosatellite DXZ4 mediates CTCF-dependent long-range intrachromosomal interactions on the human inactive X chromosome
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DOI：
10.1093/hmg/dds270
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发表时间：
2012-10-15
影响因子：
3.5
通讯作者：
Chadwick, Brian P.
中科院分区：
文献类型：
--
作者：
Horakova, Andrea H.;Moseley, Shawn C.;Chadwick, Brian P.
人类X连锁大卫星DXZ4是位于Xq23的大串联重复序列，其被包装到男性X染色体和女性活性X染色体上的异染色质中，并且响应于X染色体，失活被组织成由非活性X染色体（Xi）上的绝缘子蛋白CCCTC结合因子（CTCF）结合的常染色质。这种不寻常的表观遗传调控的目的尚不清楚，但表明DXZ4的功能具有Xi特异性增益。在Xi上可以观察到其他不太广泛的常染色质条带，但其潜在的DNA序列的身份尚不清楚。在这里，我们报告了两个新的人类X连锁串联重复序列，位于58 Mb近端和16 Mb远端的大卫星DXZ4的识别。这两个串联重复完全包含在新的剪接转录本的转录单位。与DXZ4一样，串联重复序列被包装到Xi特异性CTCF结合的常染色质中。这些序列经历频繁的CTCF依赖性的相互作用与DXZ4的Xi，暗示DXZ4作为一个表观遗传调控的Xi特异性结构元件，并提供了第一个推定的功能属性的宏卫星在人类基因组中。
The human X-linked macrosatellite DXZ4 is a large tandem repeat located at Xq23 that is packaged into heterochromatin on the male X chromosome and female active X chromosome and, in response to X chromosome, inactivation is organized into euchromatin bound by the insulator protein CCCTC-binding factor (CTCF) on the inactive X chromosome (Xi). The purpose served by this unusual epigenetic regulation is unclear, but suggests a Xi-specific gain of function for DXZ4. Other less extensive bands of euchromatin can be observed on the Xi, but the identity of the underlying DNA sequences is unknown. Here, we report the identification of two novel human X-linked tandem repeats, located 58 Mb proximal and 16 Mb distal to the macrosatellite DXZ4. Both tandem repeats are entirely contained within the transcriptional unit of novel spliced transcripts. Like DXZ4, the tandem repeats are packaged into Xi-specific CTCF-bound euchromatin. These sequences undergo frequent CTCF-dependent interactions with DXZ4 on the Xi, implicating DXZ4 as an epigenetically regulated Xi-specific structural element and providing the first putative functional attribute of a macrosatellite in the human genome.