Regulation of Sox8 through lncRNA Mrhl mediated chromatin looping in mouse spermatogonia

Abstract

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 lncRNA Mrhl in a p68-dependant manner under the control of the Wnt signalling 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. This loop 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.

Long non-coding RNAs: emerging functional players in the pathobiology and progression of myeloid leukemia

“…Lastly, a recent finding by our research group shows high expression of the lncRNA Hmrhl in the CML cell line K562 (Fatima et al, 2019;Choudhury et al, 2021). Hmrhl was discovered as a human homolog of the mouse lncRNA meiotic recombination hot spot locus (mrhl), which was also first reported by our group and has been studied extensively thereafter (Nishant et al, 2004;Ganesan and Rao, 2008;Arun et al, 2012;Akhade et al, 2014;Kataruka et al, 2017;Pal et al, 2021;Kayyar et al, 2022). With restricted expressions in the testes, liver, kidneys, and spleen, mrhl was found to be a negative regulator of Wnt signaling and a regulator of SOX8 at the chromatin level in mouse spermatogonial cells (Arun et al, 2012;Akhade et al, 2014).…”