The silencing of the one X chromosome in XX cells is mediated by XIST, a long noncoding RNA that is randomly transcribed from only one X early in development. It coats the DNA and shuts down gene expression on that X. For genes to escape, researchers hypothesize, certain sequences on the X, so-called escape elements, attract proteins that help nearby genes evade silencing. In addition, sequences known as boundary elements and their associated proteins seem to act as divisions between active and quiet regions. The identities of these regulators haven’t been conclusively pinned down, but there are several suspects.
Binding sites for YY1 are common at escapee promoters. YY1 is a transcription factor that may work in part by influencing histone acetylation, which influences gene expression.
Binding sites for CTCF (CCCTC-binding factor) are enriched in escapees as well as at the boundaries between silenced and active regions. The mechanism by which this transcription factor and manager of chromosome looping supports escape is unclear.
Topologically associated domains (TADs) distinguish segments of the genome and typically contain genes that physically interact. Researchers haven’t yet identified the nucleic acid sequences and proteins that set TAD boundaries, but the domains may help delineate silenced and escaping regions on the X.
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Amber Dance is a freelance science journalist living in the Los Angeles area. Read her work or reach out at AmberLDance.com.