A Novel Regulatory Element Regulates Human in a CTCF-Dependent Manner.

The long noncoding RNA XIST is the master regulator for the process of X chromosome inactivation (XCI) in mammalian females. Here, we report the existence of a hitherto-uncharacterized regulatory element (cRE) within the first exon of human , which determines the transcriptional status of during the initiation and maintenance phases of XCI. In the initiation phase, pluripotency factors bind to this cRE and keep repressed. In the maintenance phase of XCI, the cRE is enriched for CTCF, which activates transcription. By employing a CRISPR-dCas9-KRAB-based interference strategy, we demonstrate that binding of CTCF to the newly identified cRE is critical for regulating in a YY1-dependent manner. Collectively, our study uncovers the combinatorial effect of multiple transcriptional regulators influencing expression during the initiation and maintenance phases of XCI.