A Functional Role for the Epigenetic Regulator ING1 in Activity-induced Gene Expression in Primary Cortical Neurons

• DOI: 10.1016/j.neuroscience.2017.11.018
• Publication Date: 2017-11-21T00:19:36Z
• Authors: Laura J. Leighton; Qiongyi Zhao; Xiang Li; Chuanyang Dai; Paul R. Marshall; Sha Liu; Yi Wang; Esmi L. Zajaczkowski; Nitin Khandelwal; Arvind Kumar; Timothy W. Bredy; Wei Wei
• Keywords: 2800 Neuroscience; 0301 basic medicine; DNA repair; Muscle Proteins; ING1; Epigenesis, Genetic; 03 medical and health sciences; Animals; Humans; RNA, Messenger; Cells, Cultured; Cerebral Cortex; Neurons; epigenetics; Calcium-Binding Proteins; Intracellular Signaling Peptides and Proteins; Fibroblasts; neuronal activation; Piwi-like proteins; Mice, Inbred C57BL; Gene Expression Regulation; Gene Knockdown Techniques; Argonaute Proteins; gene regulation; Inhibitor of Growth Protein 1

AbstractEpigenetic regulation of activity-induced gene expression involves multiple levels of molecular interaction, including histone and DNA modifications, as well as mechanisms of DNA repair. Here we demonstrate that the genome-wide deposition of Inhibitor of growth family member 1 (ING1), which is a central epigenetic regulatory protein, is dynamically regulated in response to activity in primary cortical neurons. ING1 knockdown leads to decreased expression of genes related to synaptic plasticity, including the regulatory subunit of calcineurin,Ppp3r1. In addition, ING1 binding at a site upstream of the transcription start site (TSS) ofPpp3r1depends on yet another group of neuroepigenetic regulatory proteins, the Piwi-like family, which are also involved in DNA repair. These findings provide new insight into a novel mode of activity-induced gene expression, which involves the interaction between different epigenetic regulatory mechanisms traditionally associated with gene repression and DNA repair.Author contributionsL.J.L., Q.Z., T.W.B and W.W. designed the experiments. N.K., A.K., X.L., C.D., S.L. and W.W. designed and assembled shRNA constructs. L.J.L., W.W., X.L., C.D., P.R.M., E.Z., and S.L. conducted experiments. Q.Z. and Y.W. analysed ChIP-seq data. L.J.L., Q.Z., and W.W. wrote the paper. All authors reviewed and edited the manuscript.Conflicts of interestNone.