The non-canonical SMC protein SmcHD1 antagonises TAD formation and compartmentalisation on the inactive X chromosome

• DOI: 10.1038/s41467-018-07907-2
• Publication Date: 2018-12-28T11:48:22Z
• Authors: Michal R. Gdula; Tatyana B. Nesterova; Greta Pintacuda; Jonathan Godwin; Ye Zhan; Hakan Ozadam; Michael McClellan; Daniella Moralli; Felix Krueger; Catherine M. Green; Wolf Reik; Skirmantas Kriauc...; Edith Heard; Job Dekker; Neil Brockdorff
• Keywords: Epigenome

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 two mega-domains. Here we demonstrate that the non-canonical SMC family protein, SmcHD1, which is important for gene silencing on Xi, contributes to this unique architecture. Specifically, allelic mapping transcriptome epigenome SmcHD1 mutant cells reveals appearance sub-megabase defined by activation, CpG hypermethylation depletion Polycomb-mediated H3K27me3. These domains, correlate with sites enrichment Xi wild-type cells, additionally adopt features active architecture, including partial restoration TAD boundaries. architecture changes also occurred following knockout somatic cell model, but case, independent derepression. We conclude key factor defining Xi.