Chromatin structure and nuclear territories of the intergenic region between inactivated and escape genes on human inactive X chromosome.

在本研究中，我利用小鼠背景下携带活性或失活的人X染色体的人-鼠杂交细胞，阐明了失活的KLHL15与逃逸基因EIF2S3之间的染色质边界的结构和机制。主要研究结果如下：1)失活x染色体上位于KLHL15和EIF2S3之间的三个基质附着区（MAR）与核基质完全相关。2)逃逸基因EIF2S3及其侧翼区域富集了组蛋白H3K9乙酰化和组蛋白H3K4甲基化。另一方面，组蛋白H3K27和H3K9的三甲基化在失活的KLHL15上富集。这些修饰在MAR上分离。3)MAR相关蛋白复合物成员SATB1的敲低导致MAR与核基质配对和组蛋白修饰的中断。

In this study, I clarified the structure and mechanism of chromatin boundary between the inactivated KLHL15 and an escape gene, EIF2S3 by using human-mouse hybrid cells carrying either active or inactive human X chromosome in mouse background. Main findings are as follows;1) Three matrix attachment regions (MAR) located between KLHL15 and EIF2S3 in the inactive X-chromosome have been exclusively associated to nuclear matrix.2) Acetylation of histone H3K9 and methylation of histone H3K4 have been enriched at the escape gene, EIF2S3, and their flanking region. Tri-methylation of histone H3K27 and H3K9, on the other hand, have been enriched at the inactivated, KLHL15. These modifications were separated at MAR.3) Knockdown of SATB1, which is the member of MAR associated protein complex, led to the disruption of MAR and nuclear matrix pairing and histone modification.