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Epigenetics and memory: Emerging role of histone lysine methyltransferase G9a/GLP complex as bidirectional regulator
Karen Ka Lam Pang1, Mahima Sharma2, Sreedharan Sajikumar1
1Department of Physiology, 2 Medical Drive, MD9, National University of Singapore, Singapore 117593, Singapore; Neurobiology/Aging Programme, Life Sciences Institute, Centre for Life Sciences, 28 Medical Drive, Singapore 117456, Singapore.
Abstract:
Various epigenetic modifications, including histone lysine methylation, play an integral role in learning and memory. The importance of the histone lysine methyltransferase complex G9a/GLP and its associated histone H3 lysine K9 dimethylation in memory formation and cognition, has garnered the attention of researchers in the past decade. Recent studies feature G9a/GLP as the 'bidirectional regulator of synaptic plasticity', the neural correlate of memory. As the 'title' suggests, G9a/GLP participates in the maintenance of both long-term potentiation (LTP) and long-term depression (LTD). This complex is demonstrated to mostly suppress LTP-related plasticity-related products (PRPs). Notably, our recent paper also shows that G9a/GLP facilitates LTD maintenance in intact hippocampal slices - shedding light on the overlooked influence of epigenetics on LTD. Although the exact mechanisms of G9a/GLP activity regulation in cognition remain elusive, pharmacological inhibition of G9a/GLP presents a new avenue of therapeutic intervention in epigenetic dysfunction-related cognitive deficits.
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