XIST establishes inactivation across its chromosome of origin, even when expressed from autosomal transgenes, according to a new study published on BIORXiv by Dr. Carolyn Brown and PhD candidate Thomas Dixon-McDougall.
To identify the regions of human XIST essential for recruiting heterochromatic marks, the researchers generated a series of overlapping deletions in an autosomal inducible XIST transgene. They examined the ability of each construct to enrich its unified XIST territory with the histone marks established by PRC1 and PRC2 as well as the heterochromatin factors MacroH2A and SMCHD1.
PRC1 recruitment required four distinct regions of XIST, and these were completely distinct from the two domains crucial for PRC2 recruitment. Both the domains required and the impact of inhibitors suggest that PRC1 is required for SMCHD1 while PRC2 function is necessary for MacroH2A recruitment, although incomplete overlap of regions implicates a role for additional factors. The independence of the PRC1/PRC2 pathways, yet important of all regions tested, demonstrate both modularity and cooperativity across the XIST lncRNA.
