Kaixiang Cao, Ph.D
Assistant Professor
Department of Biochemistry
Department of Genetics and Genome Sciences
Case Comprehensive Cancer Center
School of Medicine, Case Western Reserve University

Histone modifications are thought to instruct gene transcription via specific reader proteins; however, recent results suggest that multiple types of histone modifications are not essential for regulating gene expression and cell identity. How histone modifications and histone modifiers function in regulating gene expression and cell fate remains enigmatic. Focusing on the mono-methylation of the lysine 4 residue on histone H3 (H3K4me1), a major enhancer mark deposited by methyltransferases MLL3/MLL4 and removed by the lysine-specific histone demethylase 1A (LSD1/KDM1A), we have previously demonstrated that LSD1 antagonizes MLL4 at enhancers to regulate gene expression and cellular differentiation, suggesting that resetting the perturbed epigenetic balance at enhancers is an effective strategy to treat diseases driven by enhancer malfunction. However, how LSD1 and H3K4me1 regulate such epigenetic balance at enhancers is largely unknown. We now utilize state-of-the-art precise genome engineering, small molecule targeting, transcriptomics, epigenomics, and stem cell biology techniques to dissect the role of LSD1 and the crosstalk of multiple epigenetic pathways in regulating transcription and cell fate. Our results suggest novel molecular mechanisms by which gene expression and cell identity are regulated and provide insight into understanding diseases driven by mis-regulation of epigenetic programs.

Hosted By: Yuhung Fan