anti-Euchromatic Histone-Lysine N-Methyltransferase 1 (EHMT1) Antibodies

Human Euchromatic Histone-Lysine N-Methyltransferase 1 (EHMT1) interaction partners

1. We report infantile onset Pulmonary hypertension (PH) and congenital heart disease despite early CHD repair in three unrelated children with Kleefstra syndrome with deletions at 9q34.3 and define a 1.24 Mb critical region containing 47 protein-coding RefSeq genes including EHMT1.

2. G9a and GLP directly bound to the alpha subunit of HIF-1 (HIF-1alpha) and catalyzed mono- and di-methylation of HIF-1alpha. The methylation suppressed HIF-1 transcriptional activity

3. In summary, it was demonstrated here that the overexpression of GLP is associated with a worse prognosis in Chronic Lymphocytic Leukemia (CLL) and that the inhibition of GLP/G9a complex leads to CLL cell death. These results suggest a potential use for GLP/G9a as markers for disease progression, as well as a promising epigenetic target for CLL treatment and prevention of disease evolution.

4. High GLP expression is associated with Ovarian Cancer metastasis.

5. The Autism spectrum disorder candidate genes SATB2, CHD8 and EHMT1 show enriched expression in neurons, especially inhibitory neurons

6. Individuals with EHMT1 mosaicism seem to have increased vulnerability for developing severe psychopathology, especially ASD and mood disorders.

7. our biochemical characterization clearly demonstrates that the previously reported two missense mutations of EHMT1 deteriorate HMT activity and GLP function, which presumably cause KS.

8. 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.

9. 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).

10. 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.

11. 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.

12. missense variants in EHMT1 that lead to protein misfolding and disrupted histone mark binding can lead to Kleefstra Syndrome [case reports]

13. 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

14. Selective degradation of the mutant EHMT1 mRNA leads to Kleefstra syndrome.

15. G9a and GLP are required for stable maintenance of imprinted DNA methylation in embryonic stem cells.

16. 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.

17. 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.

18. 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.

19. 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.

20. The expression level of EHMT1 and EHMT2 inversely correlates with the type I interferon responsiveness in chronic myeloid leukemia cell lines.

Mouse (Murine) Euchromatic Histone-Lysine N-Methyltransferase 1 (EHMT1) interaction partners

1. The euchromatic lysine methyltransferase GLP regulates heterochromatin organization and myogenic differentiation. Interestingly, GLP represses expression of the methyl-binding protein MeCP2 that induces heterochromatin clustering during differentiation.

2. reduced levels of EHMT1 protein in Ehmt1(+/-) mice does not result in general learning deficits in a touchscreen-based battery, but leads to increased adult cell proliferation in the hippocampus and enhanced pattern separation ability.

3. EHMT1 deficiency impaired neural network activity during the transition from uncorrelated background action potential firing to synchronized network bursting. Spontaneous bursting and excitatory synaptic currents were transiently reduced, whereas miniature excitatory postsynaptic currents were not affected.

4. GLP/G9a H3K9 methyltransferase complex is an enzyme counteracting Jmjd1a-mediated H3K9 demethylation at the Sry locus in gonadal somatic cells

5. miR-217-mediated, genetic, or pharmacological inactivation of EHMT1/2 was sufficient to promote pathological hypertrophy

6. EHMT1 Mediates Homeostatic Synaptic Scaling

7. The stress-induced Brg1-G9a/GLP-Dnmt3 interactions and sequence of repressive chromatin assembly on Myh6 promoter illustrates a molecular mechanism by which the heart epigenetically responds to environmental signals.

8. 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.

9. histone methyltransferase activities of GLP and G9a are stimulated by neighboring nucleosomes that are premethylated at H3K9

10. Prdm16 was required in young mice to suppress the expression of white-fat-selective genes in BAT through recruitment of the histone methyltransferase Ehmt1.

11. G9a and GLP have an essential role in normal morphogenesis of the atrioventricular septum through regulation of the size of the atrioventricular cushion.

12. Reduced Euchromatin histone methyltransferase 1 causes developmental delay, hypotonia, and cranial abnormalities associated with increased bone gene expression in Kleefstra syndrome mice.

13. EHMT1 is an essential BAT-enriched lysine methyltransferase in the PRDM16 transcriptional complex and controls brown adipose cell fate

14. These data demonstrate that Ehmt1 haploinsufficiency in mice leads to learning deficits and synaptic dysfunction, providing a possible mechanism for the ID phenotype in patients with Kleefstra syndrome

15. Metallothionein 1 h tumour suppressor activity in prostate cancer is mediated by euchromatin methyltransferase 1.

16. EHMT1 protein binds to nuclear factor-kappaB p50 and represses gene expression.

17. These studies demonstrate, for the first time, that sitagliptin exerts direct, DPP-IV-independent effects on intestinal L cells, activating cAMP and ERK1/2 signaling and stimulating total GLP-1 secretion.

18. LSH is essential for developmentally programmed de novo DNA methylation at the promoters of protein coding genes and recruitment of G9a/GLP complex to a subset of genomic loci.

19. These observations make it plausible that the Ehmt1(+/-) mouse is a faithful mammalian model for the autistic-like behavioral features of patients with the 9q34.3 subtelomeric deletion syndrome.

20. Wiz plays a major role in G9a/GLP heterodimer formation in cultured stem cells.