EHMT2

What is EHMT2?

EHMT2, a member of the histone methyltransferase family, represents a key factor in biological processes such as chromatin remodeling, gene transcription, and DNA repair. This protein possesses unique typologies and elements that play a crucial role in biomedical applications.

Initially, EHMT2, short for Euchromatic Histone Lysine Methyltransferase 2, was discovered in 2001, marked as an essential regulator in cell differentiation, proliferation, and apoptosis.

The gene locus of EHMT2 resides on chromosome 6p21.2-p21.3, identified by detailed mapping and fluorescence in situ hybridization. There are 28 Exons in the EHMT2 gene and a span of approximately 143 kb. The EHMT2 gene produces a protein of 1298 amino acids with a predicted weight of 143.5 kDa.

What Is The Structure of EHMT2 Protein?

The protein structure of EHMT2 includes multiple domains, most notably the SET domain - an enzyme domain carrying out methylation of histones that affect the gene's transcriptional activity. This domain has conserved cysteine residues and histidine residues that assist in the protein's engagement in chromatin remodeling and gene expression regulation. This multifunctional protein also contains ankyrin repeats, responsible for protein-protein interactions, helping its specific functions.

What Is The Function of EHMT2 Protein?

EHMT2 protein's primary function involves the methylation activity of transcription regulation. Specifically, it mediates the methylation of histone H3 at lysine 9 (H3K9), creating a repressive chromatin mark correlated with heterochromatin formation and gene silencing. This protein also plays a role in developmental processes, including X-chromosome inactivation in female mammals. More importantly, EHMT2 affects gene expression by organizing chromatin structure and creating an environment suitable for transcription repression.

EHMT2 protein related signal pathway

Moreover, the protein participates in signal pathways associated with cell regulation and development. It is elucidated in the regulation of signal pathways such as JAK-STAT, PI3K-Akt, and MAPK, involved in various functions - immune response, apoptosis, cell cycle, and survival. By modulating these essential cellular pathways, the EHMT2 protein enables various cellular processes' precise expression and function.

EHMT2 protein related diseases and applications

The aberrant function or expression of EHMT2 can influence numerous diseases. Its dysfunctions are associated with different types of cancer, including lung, breast, and colorectal cancers. Overexpression of EHMT2 can lead to oncogenesis due to its discovering of suppressing tumor suppressor genes. Moreover, this protein's alterations can result in neurological disorders like mental retardation and certain congenital heart diseases. This broad impact on various diseases suggests the severity of EHMT2's dysfunction and highlights its importance in maintaining regular body functions.

Clinical studies suggested that the EHMT2 protein could be leveraged as a therapeutic target for specific diseases. As its overexpression could lead to oncogenesis, the development of EHMT2 inhibitors could provide potential cancer treatments. For instance, the BIX-01294, a specific inhibitor of EHMT2, has been implied to restore tumor suppressor gene expression in cancer cells. Additionally, it can also be a potential target for therapeutic development against neurological disorders. Its modulation might ameliorate symptoms and improve life quality of patients with these conditions.

EHMT2 protein also exhibits significant potential in stem cell research. Several studies elucidated that EHMT2 could impact the pluripotency maintenance and differentiation of embryonic stem cells. By modulating EHMT2, one could potentially control stem cells in regenerative medicine applications, providing cures for various diseases and conditions.

To conclude, EHMT2 protein plays an integral role in gene transcription regulation and differentiation processes. Its involvement in diseases makes it a focal point in novel therapeutic strategies. More advanced research would illuminate further understanding of its properties and mechanisms, promising the evolution of biomedical science and applications.

Case 1: Wang J, et al. Cancer Biol Med. 2021.

The function of euchromatic histone-lysine N-methyltransferase 2 (EHMT2) has been studied in several cancers; however, little is known about its role in mantle cell lymphoma (MCL).

EHMT2 expression in MCL and reactive hyperplasia (RH) were investigated by immunohistochemistry. Co-immunoprecipitation (Co-IP) experiments were conducted to identify the proteins interacting with EHMT2.

EHMT2 was expressed in 68.57% (24/35) of MCLs but not in any RHs. Co-IP experiments revealed that EHMT2 interacted with UHRF1, HDAC1, and HDAC2 but not with HDCA3. The study determined the significance of EHMT2 in MCL and identified potential EHMT2-regulated genes.

Fig1. Interaction of EHMT2 with UHRF1 and HDACs. The schematic indicates that EHMT2 interacts with UHRF1, HDAC1, and HDAC2, but not with HDAC3.

Fig2. Changes in the H3K4, H3K9, and H3K27 methylations and EHMT2 protein levels after treatment with the EHMT2, inhibitor BIX01294. Note that H3K9me2 and H3K27me2 levels decreased with increase in drug concentration; conversely, H3K4me2 levels increased. H3K9me3 and EHMT2 showed no changes after treatment with BIX01294.

Case 2: Zeng TB, et al. PLoS Genet. 2021.

EHMT2 is the main euchromatic H3K9 methyltransferase. Embryos with zygotic, or maternal mutation in the Ehmt2 gene exhibit variable developmental delay. To understand how EHMT2 prevents variable developmental delay, the study performs a series of analysis, and establishes EHMT2 as a suppressor of transcriptional and developmental variation at the transition between gastrulation and organ specification.

Fig1. Zygotic and parental genetic deficiencies in Ehmt2 result in delayed embryo development.

(B) Images of representative embryos from crossing Ehmt2+/− parents are shown, with the embryonic days and times of collection marked to the left. The embryo names are marked at the top of each image and the somite numbers are marked underneath each image.

(E) Images of the Ehmt2mat−/+ embryos from the Ehmt2fl/fl; Zp3-creTg/0 x Ehmt2+/+ mating at E8: 9 am and E9: 9 am.

Case 3: Meng TG, et al. Int J Biol Sci. 2022.

During oocyte growth, various epigenetic modifications are gradually established, accompanied by accumulation of large amounts of mRNAs and proteins. However, little is known about the relationship between epigenetic modifications and meiotic progression. The study findings highlight the novel function of maternal EHMT2 on the metaphase I-to-anaphase I transition in mouse oocytes: regulating the transcription of Ccnb3.

Fig1. Maternal EHMT2 is essential for female fertility. (C) The signal of EHMT2 in control and Ehmt2GKOGV oocytes. (D) Breeding assays showed complete infertility of the female Ehmt2GKO mice. Continuous breeding assessment showed the cumulative number of progeny per control and Ehmt2GKO female mouse for 6 months. At least six mice were tested for each genotype. (E) The embryos generated by mating control female mice and Ehmt2GKO female mice with WT C57BL/6J male mice died before E9.5.

EHMT2 has several biochemical functions, for example, C2H2 zinc finger domain binding,histone methyltransferase activity (H3-K27 specific),histone methyltransferase activity (H3-K9 specific). Some of the functions are cooperated with other proteins, some of the functions could acted by EHMT2 itself. We selected most functions EHMT2 had, and list some proteins which have the same functions with EHMT2. You can find most of the proteins on our site.

EHMT2 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with EHMT2 here. Most of them are supplied by our site. Hope this information will be useful for your research of EHMT2.

HDAC1;RERE;MIER1;Gfi1;KAT2B;PRRC2B;PRDM5;Gug