Roles of JHDM1 in bone development and memory formation

Abstract

(PART II) Introduction: Dynamic changes in histone modification play a role in regulating the gene expression program linked to memory formation. Also, Many PTMs occur on non-histone proteins as well as histones, leading to changes in protein-protein interactions, stability, localization, and/or enzymatic activities of proteins. However, little is known about the role of JHDM1 (Jumonji-containing histone demethylases 1) as demethylase of histone or non-histone proteins. Therefore, I investigated the physiological role of JHDM1 in learning and memory in adult mice. Methods: To establish an experimental model allowing the investigation of learning and memory, 4-month-old JHDM1 transgenic mice and their wild type (WT) littermates were trained in the Morris water maze and fear-conditioning paradigm. I further examined learning and memory with JHDM1 knockdown transgenic mice by Lentivirus-Mediated RNA interfering. I tested the possibility that JHDM1 is an epigenetic regulator of target genes. Results: I found that JHDM1 transgenic mice have better ability in spatial memory formation and contextual fear conditioning compared with WT mice. Conversely, when JHDM1 was knocked down in the hippocampus, the mice showed impaired function on the hippocampus-dependent memory. The association of JHDM1 with the chromatin of CREB target genes correlated with improved memory formation. Conclusion: Taken together, these results suggest that JHDM1 has an important role in memory formation in the hippocampus. Furthermore, these findings support the notion that the JHDM1 activation might be a suitable therapeutic avenue for neurodegenerative diseases associated with learning and memory impairment