Jill Dowen lab publication featured as a highlighted article in GENETICS April 2021. A designation given to the top 1-2% of all papers in the issue.
Cohesin is one of the most mutated protein complexes in all of cancer. How may cohesin mutations contribute to cancer?
Recurrent mutations in cohesin complex members have been reported in various cancers, though it is not clear whether many cohesin sequence variants have phenotypes and contribute to disease. Here, Rittenhouse et al. utilized CRISPR/Cas9 genome editing to introduce a variety of cohesin sequence variants into murine embryonic stem cells, which provide an isogenic system for analysis of gene expression and cellular identity. The results show that some cohesin variants cause altered expression of cell identity genes and genes at insulated DNA loops. Furthermore, some cohesin variants altered the proliferation rate and differentiation potential of murine embryonic stem cells. This work shows that mutant cohesin molecules may contribute to human disease by altering gene expression programs and cellular state.
Functional impact of cancer-associated cohesin variants on gene expression and cellular identity. Rittenhouse NL, Carico ZM, Liu YF, Stefan HC, Arruda NL, Zhou J, Dowen JM. Genetics. 2021 Apr15;217(4):iyab025. doi: 10.1093/genetics/iyab025. PMID: 33704438.