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9/19(三)Chen-Yu Wang專題演講,敬請踴躍參加






講題:Investigating the role of SMCHD1 in X chromosome inactivation
講者:Chen-Yu Wang
Harvard University, Division of Medical Sciences, Boston, MA
The linear molecules of DNA that constitute our genome are wrapped around histones to form “chromatin.” To fit the nucleus, chromatin must be neatly packaged into organized structures. For instance, mammalian chromosomes are folded into two “compartments” – an active A compartment that contains actively transcribed genes, and an inactive B compartment that harbors mostly genes that are not transcribed. Interestingly, X chromosome inactivation, a process that shuts down gene expression on one of the two copies of X chromosomes in female mammals, triggers refolding of inactive X chromosome (Xi) into a unique structure that lacks compartments. How the Xi folds in this unique way has been a subject of intense investigation.
We approached this question through investigating SMCHD1, a repressive chromatin factor enriched on the Xi. We found that in female cells lacking SMCHD1, the Xi became partitioned into two large compartments. These unique compartments, which we named “S1 and S2 compartments,” are distinct from A/B compartments. We further showed that, during X-inactivation, the A/B compartments are first remodeled into S1/S2 compartments. SMCHD1 then merges S1/S2 to create the “compartment-less” Xi. In cells lacking SMCHD1, 43% of Xi genes failed to be inactivated, coinciding with aberrant distribution of Xist, a long noncoding RNA that controls X-inactivation. These data indicate that the Xi is folded in a stepwise manner, a process critical to suppress gene expression.


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