Department of Biological Science, Florida State University, Tallahassee, FL 32306-4295, USA.
Hum Mol Genet. 2012 Oct 15;21(20):4367-77. doi: 10.1093/hmg/dds270. Epub 2012 Jul 12.
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.
人类 X 连锁的大片段重复 DXZ4 位于 Xq23，是一个大串联重复序列，在雄性 X 染色体和雌性活性 X 染色体上被包装成异染色质，而在 X 染色体失活时，它被组织成由绝缘子蛋白 CCCTC 结合因子（CTCF）结合的常染色质（Xi）。这种不寻常的表观遗传调控的目的尚不清楚，但表明 DXZ4 在 Xi 上具有特定的功能增益。在 Xi 上还可以观察到其他较少的常染色质带，但潜在的 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 连锁串联重复序列的鉴定，它们位于 macrosatellite DXZ4 的近端 58Mb 和远端 16Mb 处。这两个串联重复序列完全包含在新剪接转录本的转录单元内。与 DXZ4 一样，串联重复序列被包装成 Xi 特异性的 CTCF 结合的常染色质。这些序列在 Xi 上与 DXZ4 频繁发生 CTCF 依赖性相互作用，暗示 DXZ4 是一个受表观遗传调控的 Xi 特异性结构元件，并为人类基因组中的大片段提供了第一个假定的功能属性。
