title: Histone-methyltransferase MLL2 (KMT2B) is required for memory formation in mice.
abstract: The consolidation of long-term memories requires differential gene expression. Recent research has suggested that dynamic changes in chromatin structure play a role in regulating the gene expression program linked to memory formation. The contribution of histone methylation, an important regulatory mechanism of chromatin plasticity that is mediated by the counteracting activity of histone-methyltransferases and histone-demethylases, is, however, not well understood. Here we show that mice lacking the histone-methyltransferase myeloid/lymphoid or mixed-lineage leukemia 2 (mll2/kmt2b) gene in adult forebrain excitatory neurons display impaired hippocampus-dependent memory function. Consistent with the role of KMT2B in gene-activation DNA microarray analysis revealed that 152 genes were downregulated in the hippocampal dentate gyrus region of mice lacking kmt2b. Downregulated plasticity genes showed a specific deficit in histone 3 lysine 4 di- and trimethylation, while histone 3 lysine 4 monomethylation was not affected. Our data demonstrates that KMT2B mediates hippocampal histone 3 lysine 4 di- and trimethylation and is a critical player for memory formation.
authors: Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, 37077 Göttingen, Germany.
authors: Cemil
authors: C
authors: Kerimoglu
authors: Roberto C
authors: RC
authors: Agis-Balboa
authors: Andrea
authors: A
authors: Kranz
authors: Roman
authors: R
authors: Stilling
authors: Sanaz
authors: S
authors: Bahari-Javan
authors: Eva
authors: E
authors: Benito-Garagorri
authors: Rashi
authors: R
authors: Halder
authors: Susanne
authors: S
authors: Burkhardt
authors: Adrian Francis
authors: AF
authors: Stewart
authors: Andre
authors: A
authors: Fischer
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D006624:Hippocampus / Q000201:enzymology; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000172:deficiency / Q000235:genetics; D018782:Maze Learning / Q000502:physiology; D057567:Memory, Long-Term / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009363:Neoplasm Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D009473:Neuronal Plasticity / Q000235:genetics / Q000502:physiology
chemical_list: D004268:DNA-Binding Proteins; C120898:KMT2D protein, human; D009363:Neoplasm Proteins; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase