I would like to cordially invite you to the next Nencki Institute seminar which will take place online on the 13th of January at 3pm. Dr. Michal Gdula, who is a head of the Developmental Epigenetics lab at the Institute of Molecular Biology and Biotechnology at the Faculty of Biology/Centre of Advanced Technology of the Adam Mickiewicz University in Poznań, will give a lecture entitled: How to shut down a whole chromosome? SmcHD1, epigenetics and 4D genome in X inactivation.
X chromosome inactivation is the mechanism that evolved in mammals to equalize levels of X-linked gene expression in XX females relative to XY males. Cells of early female embryos selectively inactivate a single X chromosome, usually at random, resulting in the formation of a stable heterochromatic structure, the Barr body. The inactive X chromosome (Xi), once established, is highly stable, and is maintained in somatic cells throughout the lifetime of the animal. The inactive X chromosome (Xi) in female mammals adopts an atypical higher-order chromatin structure, manifested as a global loss of local topologically associated domains (TADs), A/B compartments and formation of two mega-domains. The non-canonical SMC family protein, SmcHD1, which is important for gene silencing on Xi, contributes to this unique chromosome architecture. Specifically, allelic mapping of the transcriptome and epigenome in SmcHD1 mutant cells reveals the appearance of sub-megabase domains defined by gene activation, CpG hypermethylation and depletion of Polycomb-mediated H3K27me3. These domains, which correlate with sites of SmcHD1 enrichment on Xi in wild-type cells, additionally adopt features of active X chromosome higher-order chromosome architecture, including A/B compartments and partial restoration of TAD boundaries. Xi chromosome architecture changes also occurred following SmcHD1 knockout in a somatic cell model, but in this case, independent of Xi gene derepression. SmcHD1 is a key factor in defining the unique chromosome architecture of Xi.