WEHI Genetics and Gene Regulation Special Seminar hosted by Professor Marnie Blewitt

Shifeng Xue

Assistant Professor – Department of Biological Sciences, National University of Singapore

One Gene, Two Diseases: SMCHD1’s Role in Epigenetic Repression and Human Health                    

L7W Seminar Room

Join via TEAMS

Including Q&S session

In every cell, only a small fraction of the genome is active at any one point. My research focuses on how parts of the genome are kept silent. My talk will centre on SMCHD1, an epigenetic repressor. SMCHD1 is essential for X chromosome inactivation in mammalian females and regulates other autosomal targets. Strikingly, mutations in SMCHD1 cause two seemingly unrelated diseases: facioscapulohumeral muscular dystrophy (FSHD), a progressive muscle-wasting disorder, and Bosma arhinia microphthalmia syndrome (BAMS), a developmental condition where infants are born without a nose.

In this talk, I will unravel how SMCHD1’s molecular functions connect to these pathologies. First, I will explore its biophysical mechanism: SMCHD1 compacts DNA and chromatin through multivalent bridging, forming protein-DNA clusters that enforce long-range repression. Next, I will link this mechanism to BAMS pathology. Using patient-derived stem cells, we discovered that SMCHD1 mutations disrupt cranial placode differentiation, a cell type essential for nose and sensory organ development. Finally, I will reveal SMCHD1’s unexpected role in spermatogonial stem cell maintenance.
 

By bridging single-molecule biophysics, developmental biology, and stem cell epigenetics, this work redefines SMCHD1 as a master regulator of genome organization and underscores the importance of epigenetic repression in development and disease.

Shifeng Xue is an Assistant Professor in the Department of Biological Sciences at National University of Singapore. She received her PhD in Developmental Biology from University of California, San Francisco and completed postdoctoral training in Human Genetics at A*STAR Singapore. Her laboratory uses human pluripotent stem cells, zebrafish and mouse to study rare genetic diseases, connecting genotype to developmental phenotypes with mechanistic insights. 

All welcome!