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Sox8  is a developmentally important transcription factor that plays an important role in sex maintenance and fertility of adult mice. In the B-type spermatogonial cells,  Sox8  is regulated by the long noncoding RNAs (lncRNA)  Mrhl  in a p68-dependant manner under the control of the Wnt signaling pathway. The downregulation of  Mrhl  leads to the meiotic commitment of the spermatogonial cells in a  Sox8 -dependant manner. While the molecular players involved in the regulation of transcription at the  Sox8  promoter have been worked out, our current study points to the involvement of the architectural proteins CTCF and cohesin in mediating a chromatin loop that brings the  Sox8  promoter in contact with a silencer element present within the gene body in the presence of lncRNA  Mrhl  concomitant with transcriptional repression. Further, lncRNA  Mrhl  interacts with the  Sox8  locus through the formation of a DNA:DNA:RNA triplex, which is necessary for the recruitment of PRC2 to the locus. The downregulation of lncRNA  Mrhl  results in the promoter-silencer loop giving way to a promoter-enhancer loop. This active transcription-associated chromatin loop is mediated by YY1 and brings the promoter in contact with the enhancer present downstream of the gene.

Regulation of Sox8 through lncRNA Mrhl -Mediated Chromatin Looping in Mouse Spermatogonia