TY  - JOUR
AU  - Kerimoglu, Cemil
AU  - Sakib, M Sadman
AU  - Jain, Gaurav
AU  - Benito, Eva
AU  - Burkhardt, Susanne
AU  - Capece, Vincenzo
AU  - Kaurani, Lalit
AU  - Halder, Rashi
AU  - Agís-Balboa, Roberto Carlos
AU  - Stilling, Roman
AU  - Urbanke, Hendrik
AU  - Kranz, Andrea
AU  - Stewart, A Francis
AU  - Fischer, Andre
TI  - KMT2A and KMT2B Mediate Memory Function by Affecting Distinct Genomic Regions.
JO  - Cell reports
VL  - 20
IS  - 3
SN  - 2211-1247
CY  - [New York, NY]
PB  - Elsevier
M1  - DZNE-2020-05708
SP  - 538-548
PY  - 2017
AB  - 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.
KW  - Animals
KW  - Gene Expression Regulation, Enzymologic
KW  - Hippocampus: enzymology
KW  - Histone-Lysine N-Methyltransferase: biosynthesis
KW  - Histone-Lysine N-Methyltransferase: genetics
KW  - Memory
KW  - Methylation
KW  - Mice
KW  - Myeloid-Lymphoid Leukemia Protein: biosynthesis
KW  - Myeloid-Lymphoid Leukemia Protein: genetics
KW  - Neurons: enzymology
KW  - Myeloid-Lymphoid Leukemia Protein (NLM Chemicals)
KW  - Histone-Lysine N-Methyltransferase (NLM Chemicals)
KW  - Kmt2a protein, mouse (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:28723559
DO  - DOI:10.1016/j.celrep.2017.06.072
UR  - https://pub.dzne.de/record/139386
ER  -