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The non-canonical SMC protein SmcHD1 antagonises TAD formation and compartmentalisation on the inactive X chromosome
- Source :
- Nature Communications, Vol 10, Iss 1, Pp 1-14 (2019), Nature Communications, Nature Communications, Nature Publishing Group, 2019, 10 (1), pp.30. ⟨10.1038/s41467-018-07907-2⟩
- Publication Year :
- 2018
- Publisher :
- Nature Research, 2018.
-
Abstract
- 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. Here we demonstrate that 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. We conclude that SmcHD1 is a key factor in defining the unique chromosome architecture of Xi.<br />The inactive X chromosome (Xi) has an atypical structure, with global loss of TADs, A/B compartments and formation of mega-domains. Here the authors show that the non-canonical SMC family protein, SmcHD1, important for developmental gene silencing on Xi, antagonises TAD formation and compartmentalization on the Xi in a transcription independent way.
- Subjects :
- Male
Transcriptional Activation
Chromosomal Proteins, Non-Histone
Science
[SDV]Life Sciences [q-bio]
Polycomb-Group Proteins
Exons
DNA Methylation
Fibroblasts
Article
Cell Line
Histones
Gene Knockout Techniques
Mice
X Chromosome Inactivation
Animals
Point Mutation
CpG Islands
Female
lcsh:Q
CRISPR-Cas Systems
lcsh:Science
Alleles
Subjects
Details
- ISSN :
- 20411723
- Database :
- OpenAIRE
- Journal :
- Nature Communications, Vol 10, Iss 1, Pp 1-14 (2019), Nature Communications, Nature Communications, Nature Publishing Group, 2019, 10 (1), pp.30. ⟨10.1038/s41467-018-07907-2⟩
- Accession number :
- edsair.doi.dedup.....386ef50533042fed11ca2f1148afaf36