Journal Article DZNE-2020-05708

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KMT2A and KMT2B Mediate Memory Function by Affecting Distinct Genomic Regions.

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2017
Elsevier [New York, NY]

Cell reports 20(3), 538-548 () [10.1016/j.celrep.2017.06.072]

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Abstract: 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.

Keyword(s): Animals (MeSH) ; Gene Expression Regulation, Enzymologic (MeSH) ; Hippocampus: enzymology (MeSH) ; Histone-Lysine N-Methyltransferase: biosynthesis (MeSH) ; Histone-Lysine N-Methyltransferase: genetics (MeSH) ; Memory (MeSH) ; Methylation (MeSH) ; Mice (MeSH) ; Myeloid-Lymphoid Leukemia Protein: biosynthesis (MeSH) ; Myeloid-Lymphoid Leukemia Protein: genetics (MeSH) ; Neurons: enzymology (MeSH) ; Myeloid-Lymphoid Leukemia Protein ; Histone-Lysine N-Methyltransferase ; Kmt2a protein, mouse

Classification:

Contributing Institute(s):
  1. Epigenetics and Systems Medicine in Neurodegenerative Diseases (AG Fischer)
  2. Computational Systems Biology (AG Bonn 2)
  3. Genome Dynamics in Neurodegenerative Diseases (AG Sananbenesi)
  4. Göttingen common (Göttingen common)
Research Program(s):
  1. 342 - Disease Mechanisms and Model Systems (POF3-342) (POF3-342)

Appears in the scientific report 2017
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Medline ; Creative Commons Attribution-NonCommercial-NoDerivs CC BY-NC-ND 4.0 ; DOAJ ; OpenAccess ; BIOSIS Previews ; Clarivate Analytics Master Journal List ; DOAJ Seal ; IF >= 5 ; JCR ; SCOPUS ; Web of Science Core Collection
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Institute Collections > GÖ DZNE > GÖ DZNE-Göttingen common
Institute Collections > GÖ DZNE > GÖ DZNE-AG Sananbenesi
Document types > Articles > Journal Article
Institute Collections > GÖ DZNE > GÖ DZNE-AG Fischer
Institute Collections > GÖ DZNE > GÖ DZNE-AG Bonn 2
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 Record created 2020-02-18, last modified 2024-03-14


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