In our latest paper, we investigate the KDM1a gene (also known as LSD1) and its role as a regulator of transcription at enhancers. We show that KDM1A actively maintains the optimal enhancer status in both undifferentiated and lineage-committed mouse embryonic stem cells (mESCs). In Kdm1a-deficient mESCs, a large fraction of these enhancers gains additional H3K4 methylation, which is accompanied by increases in H3K27 acetylation and increased expression of both enhancer RNAs (eRNAs) and target genes. In postmitotic neurons, loss of KDM1A leads to premature activation of neuronal activity-dependent enhancers and genes. Taken together, these results suggest that KDM1A is a versatile regulator of enhancers and acts as a rheostat to maintain optimal enhancer activity by counterbalanc- ing H3K4 methylation at enhancers.
Former postdoc Saurabh Agarwal; PhD students Katie Bonefas, Tricia Garay, and Bobby Porter; and postdoc Yumie Nakamura all contributed to this study. A true lab-team effort!
Read the paper here: