SMCHD1 maintains heterochromatin, genome compartments and epigenome landscape in human myoblasts
Abstract Mammalian genomes are subdivided into euchromatic A compartments that contain mostly active chromatin, and inactive, heterochromatic B compartments. However, it is not well understood how A and B genome compartments are established and maintained. Here we study SMCHD1, an SMC-like protein b...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-07-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-62211-0 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849332540843753472 |
|---|---|
| author | Zhijun Huang Wei Cui Ishara Ratnayake Kristin L. Gallik Lorna Cohen Rabi Tawil Gerd P. Pfeifer |
| author_facet | Zhijun Huang Wei Cui Ishara Ratnayake Kristin L. Gallik Lorna Cohen Rabi Tawil Gerd P. Pfeifer |
| author_sort | Zhijun Huang |
| collection | DOAJ |
| description | Abstract Mammalian genomes are subdivided into euchromatic A compartments that contain mostly active chromatin, and inactive, heterochromatic B compartments. However, it is not well understood how A and B genome compartments are established and maintained. Here we study SMCHD1, an SMC-like protein best known for its role in X chromosome inactivation, in human male myoblasts. SMCHD1 colocalizes with Lamin B1 and the heterochromatin mark H3K9me3. Loss of SMCHD1 leads to extensive heterochromatin and Lamin B1 depletion at the nuclear lamina, acquisition of active chromatin states and increased DNA methylation along chromosomes. In absence of SMCHD1, long range intra-chromosomal contacts between B compartments are lost while many new TADs and loops are formed. Inactivation of SMCHD1 promotes numerous B to A compartment transitions accompanied by activation of silenced genes. The data suggests that SMCHD1 functions as an anchor for heterochromatin domains at the nuclear lamina ensuring that these domains are poorly accessible to DNA methyltransferases and to epigenome modification enzymes that typically operate in active chromatin. Thus, the properties of SMCHD1 in heterochromatin maintenance extend well beyond its role in X chromosome inactivation. |
| format | Article |
| id | doaj-art-86a974eab59a4eb5859c98ce515b1fa0 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-86a974eab59a4eb5859c98ce515b1fa02025-08-20T03:46:09ZengNature PortfolioNature Communications2041-17232025-07-0116112110.1038/s41467-025-62211-0SMCHD1 maintains heterochromatin, genome compartments and epigenome landscape in human myoblastsZhijun Huang0Wei Cui1Ishara Ratnayake2Kristin L. Gallik3Lorna Cohen4Rabi Tawil5Gerd P. Pfeifer6Department of Epigenetics, Van Andel InstituteDepartment of Epigenetics, Van Andel InstituteCryo-EM Core, Van Andel InstituteOptical Imaging Core, Van Andel InstituteOptical Imaging Core, Van Andel InstituteDepartment of Neurology, University of Rochester Medical CenterDepartment of Epigenetics, Van Andel InstituteAbstract Mammalian genomes are subdivided into euchromatic A compartments that contain mostly active chromatin, and inactive, heterochromatic B compartments. However, it is not well understood how A and B genome compartments are established and maintained. Here we study SMCHD1, an SMC-like protein best known for its role in X chromosome inactivation, in human male myoblasts. SMCHD1 colocalizes with Lamin B1 and the heterochromatin mark H3K9me3. Loss of SMCHD1 leads to extensive heterochromatin and Lamin B1 depletion at the nuclear lamina, acquisition of active chromatin states and increased DNA methylation along chromosomes. In absence of SMCHD1, long range intra-chromosomal contacts between B compartments are lost while many new TADs and loops are formed. Inactivation of SMCHD1 promotes numerous B to A compartment transitions accompanied by activation of silenced genes. The data suggests that SMCHD1 functions as an anchor for heterochromatin domains at the nuclear lamina ensuring that these domains are poorly accessible to DNA methyltransferases and to epigenome modification enzymes that typically operate in active chromatin. Thus, the properties of SMCHD1 in heterochromatin maintenance extend well beyond its role in X chromosome inactivation.https://doi.org/10.1038/s41467-025-62211-0 |
| spellingShingle | Zhijun Huang Wei Cui Ishara Ratnayake Kristin L. Gallik Lorna Cohen Rabi Tawil Gerd P. Pfeifer SMCHD1 maintains heterochromatin, genome compartments and epigenome landscape in human myoblasts Nature Communications |
| title | SMCHD1 maintains heterochromatin, genome compartments and epigenome landscape in human myoblasts |
| title_full | SMCHD1 maintains heterochromatin, genome compartments and epigenome landscape in human myoblasts |
| title_fullStr | SMCHD1 maintains heterochromatin, genome compartments and epigenome landscape in human myoblasts |
| title_full_unstemmed | SMCHD1 maintains heterochromatin, genome compartments and epigenome landscape in human myoblasts |
| title_short | SMCHD1 maintains heterochromatin, genome compartments and epigenome landscape in human myoblasts |
| title_sort | smchd1 maintains heterochromatin genome compartments and epigenome landscape in human myoblasts |
| url | https://doi.org/10.1038/s41467-025-62211-0 |
| work_keys_str_mv | AT zhijunhuang smchd1maintainsheterochromatingenomecompartmentsandepigenomelandscapeinhumanmyoblasts AT weicui smchd1maintainsheterochromatingenomecompartmentsandepigenomelandscapeinhumanmyoblasts AT ishararatnayake smchd1maintainsheterochromatingenomecompartmentsandepigenomelandscapeinhumanmyoblasts AT kristinlgallik smchd1maintainsheterochromatingenomecompartmentsandepigenomelandscapeinhumanmyoblasts AT lornacohen smchd1maintainsheterochromatingenomecompartmentsandepigenomelandscapeinhumanmyoblasts AT rabitawil smchd1maintainsheterochromatingenomecompartmentsandepigenomelandscapeinhumanmyoblasts AT gerdppfeifer smchd1maintainsheterochromatingenomecompartmentsandepigenomelandscapeinhumanmyoblasts |