Faculty of Life Science and Technology, Kunming University of Science and Technology, 727 South Jingming Road, Chenggong District, Kunming, Yunnan Province, 650500, China.
Faculty of Life Science and Technology, Kunming University of Science and Technology, 727 South Jingming Road, Chenggong District, Kunming, Yunnan Province, 650500, China; Yunnan Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, No. 1 Boda Road, Yuhua Area, Chenggong District, Kunming, Yunnan, 650500, China.
Biochem Biophys Res Commun. 2018 Jun 12;500(4):852-859. doi: 10.1016/j.bbrc.2018.04.173. Epub 2018 May 1.
The spatiotemporal control of HOX gene expression is dependent on positional identity and often correlated to their genomic location within each loci. Maintenance of HOX expression patterns is under complex transcriptional and epigenetic regulation, which is not well understood. Here we demonstrate that HOTTIP, a lincRNA transcribed from the 5' edge of the HOXA locus, physically associates with the CCCTC-binding factor (CTCF) that serves as an insulator by organizing HOXA cluster into disjoint domains, to cooperatively maintain the chromatin modifications of HOXA genes and thus coordinate the transcriptional activation of distal HOXA genes in human foreskin fibroblasts. Our results reveal the functional connection of HOTTIP and CTCF, and shed light on lincRNAs in gene activation and CTCF mediated chromatin organization.
HOX 基因表达的时空调控依赖于位置身份，并且通常与其在每个基因座内的基因组位置相关。HOX 表达模式的维持受到复杂的转录和表观遗传调控的影响，但目前对此了解甚少。在这里，我们证明了 HOTTIP，一种从 HOXA 基因座 5'端转录的 lincRNA，通过将 HOXA 簇组织成不连续的域，与作为绝缘子的 CCCTC 结合因子 (CTCF) 物理结合，以协同维持 HOXA 基因的染色质修饰，从而协调人包皮成纤维细胞中远端 HOXA 基因的转录激活。我们的结果揭示了 HOTTIP 和 CTCF 的功能联系，并阐明了 lincRNA 在基因激活和 CTCF 介导的染色质组织中的作用。
