Fig. 7: Working model on the regulatory role of Xist during XCI maintenance. | Nature Communications

Fig. 7: Working model on the regulatory role of Xist during XCI maintenance.

From: Xist exerts gene-specific silencing during XCI maintenance and impacts lineage-specific cell differentiation and proliferation during hematopoiesis

Fig. 7: Working model on the regulatory role of Xist during XCI maintenance.

Transcription of X-linked genes during XCI maintenance is regulated by Xist-dependent and Xist-independent mechanisms. Xist is required for maintaining H3K27me3 occupancy across Xi and limiting chromatin accessibility and H3K27ac deposition surrounding Xist-dependent genes. Low H3K27me3 occupancy and high chromatin accessibility at the basal state predispose XCI escape genes to be highly susceptible to transcriptional upregulation upon Xist loss. Increased chromatin accessibility on the Xi allows for higher binding frequency for transcriptional factors, such as YY1. While promoter-specific YY1 binding either activates or represses transcription, enhancer-specific YY1 binding might facilitate transcription through regulation of promoter–enhancer interactions within TAD-like structures at regions harboring XCI escape genes in Xist-deficient cells. Our findings support a model in which Xist-deficiency phenotypes in different cell lineages or tissues are influenced by cell type-specific characteristics including variability in types of XCI escape genes, cell turnover rate and availability of TFs.

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