SMCHD1 is required for chromosome to adopt conformation that suppresses gene expression. A research team has identified the essential role of a structural protein in the silencing of the inactive X chromosome, a process that prevents both copies of the same gene from being expressed in female mammals, which carry two copies of the X chromosome. The study was published in the journal Cell.
Research team has identified the essential role of a structural protein in the silencing of the inactive X chromosome, a process that prevents both copies of the same gene from being expressed in female mammals, which carry two copies of the X chromosome. The investigators describe finding that the SMCHD1 protein is required for the inactive X chromosome to be processed in a way that blocks the expression of its genes.
They showed that the SMCHD1 protein influences gene expression by regulating the folding of the inactive X chromosome into its unique conformation, which prevents expression of its genes.
X chromosome inactivation
It occurs in early embryonic development reconfigures chromatin into a unique formation through the mediation of a large RNA molecule called Xist. The spreading of Xist across the chromosome induces it to fold into two large structural domains, which then merge into a "compartment-less" structure that suppresses transcription of the genes on the chromosome.
To investigate protein factors that may regulate the process of X inactivation, the team focused on the SMC family of structural proteins, which are known to regulate chromosome conformation. Previous studies found that SMCHD1 was highly enriched on inactive X chromosomes and appeared to be critical to the inactivation process.
They then found that the loss of SMCHD1 prevented the spreading of Xist across the chromosome and kept the two large domains, which the team named S1 and S2 compartments, from being merged into the typical compartment-less inactive X structure. By bridging the S1 and S2 compartments, SMCHD1 was found to induce their merging into the conformation that prevents gene expression. Without the protein, the two compartments persist, allowing the expression of about 40 percent of the genes on what should be an inactive chromosome.
They know that certain X chromosome genes are particularly sensitive to the loss of SMCHD1, so in the future we may be able to harness that differential sensitivity to turn on specific genes.