New studies from the Jia lab reveal detailed mechanisms of chromatin-based epigenetic inheritance
In a study featured on the cover of the September 5th issue of Molecular Cell, researchers from the Department of Biological Sciences, led by Dr. Songtao Jia, have uncovered key insights into the mechanism of epigenetic inheritance - a process where gene expression patterns are passed down through generations independently of DNA sequence. Epigenetic inheritance plays crucial roles in determining cell identity, and its misregulation has been linked to developmental diseases and various cancers.
Histones, the proteins that package DNA into chromatin, are the primary carriers of epigenetic information. These proteins are frequently modified by chemical groups, and specific modifications are enriched at distinct genomic locations to regulate gene expression. During DNA replication, modified histones are symmetrically distributed to daughter DNA strands, serving as templates to replicate chromatin structure and preserve gene activity memory in both daughter cells. However, the exact mechanism of parental histone segregation remains elusive.
A major challenge in studying epigenetic inheritance has been the lack of experimental systems that directly measure the efficiency of this process. Earlier this year, the Jia lab published a paper in Genes & Development that introduced novel assays in fission yeast to measure the transmission efficiency of heterochromatin - a silenced gene expression state - as a proxy for epigenetic inheritance. In their latest Molecular Cell paper, the Jia lab used these assays to perform genetic screens and discovered a novel regulator, Mrc1, which is part of the DNA replication machinery. To further investigate the mechanism, the Jia lab collaborated with Dr. Zhiguo Zhang at CUIMC and Dr. Liang Tong and Dr. Marko Jovanovic within the department. Together, they found that Mrc1 acts as a physical barrier, separating the pathways for leading and lagging strand parental histone segregation and promotes parental histone segregation to the lagging strand.
In parallel, the Jia lab partnered with Dr. Danesh Moazed’s lab at Harvard Medical School and published a second paper in the September 5th issue of Cell. This study revealed additional roles of Mrc1 in the regulation of epigenetic inheritance.
Together, these two papers provide a detailed mechanism of parental histone segregation. It offers insights how about epigenetic inheritance needs to be tightly regulated, such as during the asymmetric division of stem cells. The findings also highlight potential new targets for interventions aimed at reprogramming or controlling epigenetic processes.
Note: ChatGPT was used in the editing of this article.