KMT2A and KMT2B Mediate Memory Function by Affecting Distinct Genomic Regions

Publication date: 18 July 2017
Source:Cell Reports, Volume 20, Issue 3
Author(s): Cemil Kerimoglu, M. Sadman Sakib, Gaurav Jain, Eva Benito, Susanne Burkhardt, Vincenzo Capece, Lalit Kaurani, Rashi Halder, Roberto Carlos Agís-Balboa, Roman Stilling, Hendrik Urbanke, Andrea Kranz, A. Francis Stewart, Andre Fischer
Kmt2a and Kmt2b are H3K4 methyltransferases of the Set1/Trithorax class. We have recently shown the importance of Kmt2b for learning and memory. Here, we report that Kmt2a is also important in memory formation. We compare the decrease in H3K4 methylation and de-regulation of gene expression in hippocampal neurons of mice with knockdown of either Kmt2a or Kmt2b. Kmt2a and Kmt2b control largely distinct genomic regions and different molecular pathways linked to neuronal plasticity. Finally, we show that the decrease in H3K4 methylation resulting from Kmt2a knockdown partially recapitulates the pattern previously reported in CK-p25 mice, a model for neurodegeneration and memory impairment. Our findings point to the distinct functions of even closely related histone-modifying enzymes and provide essential insight for the development of more efficient and specific epigenetic therapies against brain diseases.

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Teaser

Kerimoglu et al. report that the related histone methyltransferases Kmt2a and Kmt2b are both required for memory function but control different neuronal gene-expression programs. Loss of Kmt2a partially recapitulates changes in H3K4me3 seen in Alzheimer's models.


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