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The Autism spectrum disorder candidate genes SATB2, CHD8 and EHMT1 show enriched expression in neurons, especially inhibitory neurons
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Individuals with EHMT1 mosaicism seem to have increased vulnerability for developing severe psychopathology, especially ASD and mood disorders.
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our biochemical characterization clearly demonstrates that the previously reported two missense mutations of EHMT1 deteriorate HMT activity and GLP function, which presumably cause KS.
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Neurodevelopmental disorders may be related to deficits in activity-dependent wiring of brain circuits during development. Although Kleefstra syndrome has been associated with dendritic and synaptic defects in mice and Drosophila, little is known about the role of EHMT1 in the development of cortical neuronal networks. We investigated the impact of EHMT1 deficiency at the network and single cell level.
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These results suggest that EHMT2 downregulation in CD4(+) T-cells may be linked to a protection mechanism against the development of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP).
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Regulated methylation and phosphorylation serve as a switch controlling G9a and GLP coactivator function, suggesting that this mechanism may be a general paradigm for directing specific transcription factor and coregulator actions on different genes.
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trr and G9a also have common direct targets, including the Drosophila ortholog of Arc (Arc1), a key regulator of synaptic plasticity. Our data highlight the clinical and molecular convergence between the KMT2 and EHMT protein families, which may contribute to a molecular network underlying a larger group of intellectual disability / autism spectrum disorder -related disorders.
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missense variants in EHMT1 that lead to protein misfolding and disrupted histone mark binding can lead to Kleefstra Syndrome [case reports]
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we find an estrogen receptor-independent synthetic lethal interaction between a GATA3 frameshift mutant with an extended C-terminus and the histone methyltransferases G9A and GLP, indicating perturbed epigenetic regulation
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Selective degradation of the mutant EHMT1 mRNA leads to Kleefstra syndrome.
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G9a and GLP are required for stable maintenance of imprinted DNA methylation in embryonic stem cells.
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the clinical picture we found in Norwegian patients with Kleefstra syndrome is similar to the findings described in the literature. An interesting point is that in the literature >85% of the patients have a deletion of 9q34.3 and the remaining have a mutation in the EHMT1 gene, whereas in this study we found 50% with a deletion, and 50% with a mutation.
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This study demonstrate that the increases in a restrictive epigenome seen in schizophrenia are sex dependent. Specifically,H3K9me2 were significantly increased in lymphocytes from men with schizophrenia.
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Data indicate zinc finger proteins ZNF644 and WIZ as two core subunits in the histone-lysine N-methyltransferase G9a/GLP complex, and interact with the transcription activation domain of G9a and GLP.
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data provide genetic and pharmacologic evidence that EHMT1 and EHMT2 are epigenetic regulators involved in gamma-globin repression and represent a novel therapeutic target for SCD.
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The expression level of EHMT1 and EHMT2 inversely correlates with the type I interferon responsiveness in chronic myeloid leukemia cell lines.
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The current knowledge on the mechanisms of action and function of EHMT1, with particular emphasis on their interplay in the regulation of chromatin states and biological processes.
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Haploinsufficiency of EHMT1 caused by either microdeletions at 9q34.3 or intragenic mutations are associated with Kleefstra syndrome.
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PRC2 and G9a/GLP interact physically and functionally.
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Data indicate that Kleefstra syndrome patient carrying a splice-site mutation in EHMT1 inherited from the mother who showed tissue-specific mosaicism.
