China
Africa
Explore chapters and articles related to this topic
Role of Histone Methyltransferase in Breast Cancer
Published in Meenu Gupta, Rachna Jain, Arun Solanki, Fadi Al-Turjman, Cancer Prediction for Industrial IoT 4.0: A Machine Learning Perspective, 2021
Surekha Manhas, Zaved Ahmed Khan
G9a is a protein that consists of 1263 amino acids with many distinct domains. Due to the lack of DNA-binding domain in G9a, it specifically relies on cofactors for its localization. The C-terminal dependent SET domain must have the activity of enzyme lysine methyltransferase, which specifically defines major functions of this protein family. G9a SET domain has the potential to mono-/dimethylate H3K9; still, it is the least efficient to mediate trimethylation [97]. Consistent with this, G9a deletion results in global H3K9me2 reduction [84,93]. Unlike other members associated with the SET domain, G9a has specific domains that provide additional functions. First, G9a shows resemblance with drosophila notch because of eight series of 33-amino acid repeats [92].
Sotos Syndrome
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
Mapped to chromosome 5q35.3, the nuclear receptor-binding SET domain protein 1 gene (NSD1) comprises 23 exons, which generate a 12.0 kb transcript, and encodes a 2596-aa protein (NSD1, a histone-lysine N-methyltransferase with H3 lysine-36 and H4 lysine-20 specificity; also known as androgen receptor-associated coregulator 267 or ARA267), which consists of at least 12 functional domains, including 2 nuclear receptor interaction domains (NID−L and NID+L), 2 proline-tryptophan-tryptophan-proline (PWWP) domains, 5 plant homeodomains (PHD), a conserved SET (su-var 3–9, enhancer of zeste, trithorax) domain, and a SET domain−associated cysteine-rich (SAC) domain (Table 98.1).
Applications of imaging genomics beyond oncology
Published in Ruijiang Li, Lei Xing, Sandy Napel, Daniel L. Rubin, Radiomics and Radiogenomics, 2019
Xiaohui Yao, Jingwen Yan, Li Shen
Genetic factors were found to play a major role in the etiology of schizophrenia. A meta-analysis using pooled data from 12 twin studies estimated the heritability of schizophrenia to be approximately 80% [107]. To date, around 30 schizophrenia-associated loci have been identified through GWAS to play a role in conferring the risk of schizophrenia, such as catechol-O-methyltransferase (COMT), Disrupted In Schizophrenia 1 (DISC1), regulator of G protein signaling 4 (RGS4), neuregulin 1 (NRG1), dystrobrevin binding protein 1 (DTNBP1), D-amino acid oxidase activator (DAOA), phosphodiesterase 4B (PDE4B), Dopamine- and cAMP-regulated phosphoprotein, Mr 32 kDa (DARPP-32) protein phosphatase 1 regulatory subunit 3B and glutamate metabotropic receptor 3 (GRM3) [108]. There are also growing evidences from exome sequencing studies indicating that some risk genes and pathways are affected by both common and rare variants [109], which implies large effects of rare variants on individual risk. This can be best exemplified by 11 large, rare recurrent CNVs and loss-of-function variants in set domain containing 1A, histone lysine methyltransferase (SETD1A) [109,110]. Evidences from other exome sequencing studies imply more other rare variants conferring substantial individual risk [111,112]. Despite the remarkable progress in the search for risk genes associated with schizophrenia, translation of genetic associations into targetable mechanisms related to disease pathogenesis remains poorly understood.
SETD2 detection may reveal response to induction therapy and survival profile in acute myeloid leukemia patients
Published in Hematology, 2023
SET domain containing protein 2 (SETD2), a histone methyltransferase of H3K36, promotes DNA repair via methylation of H3K36 under DNA double-strand break [11]. Recent studies show that SETD2 is involved in the initiation and progression of several hematological malignancies [12, 13]. For instance, SETD2 knockout mice exhibit a reduced number of hematopoietic stem and progenitor cells (HSPCs) with increased apoptosis potency [12]. However, another study reports that SETD2 deletion impairs the differentiation and self-renewal of HSPCs, leading to the malignant transformation toward myelodysplastic syndrome [13]. Furthermore, reduced SETD2 is also implied in the development of chemotherapy resistance in leukemia [14, 15]. Given that SETD2 plays such a critical role in leukemia, it is reasonable to hypothesize that SETD2 may also exhibit certain clinical value in AML patients, while the relevant study is limited.
The role of sialic acid-binding immunoglobulin-like-lectin-1 (siglec-1) in immunology and infectious disease
Published in International Reviews of Immunology, 2023
Shane Prenzler, Santosh Rudrawar, Mario Waespy, Sørge Kelm, Shailendra Anoopkumar-Dukie, Thomas Haselhorst
The sialic acid binding immunoglobulin-like lectins (Siglec) are a family of transmembrane proteins characterized by an extracellular domain, the transmembrane region and cytoplasmic tail [1]. Sialic acids are a family of nine-carbon acidic monosaccharides that occur naturally at the end of sugar chains attached to the surfaces of cells and soluble proteins and are ligands for Siglec proteins (Figure 1) [2]. Siglec-1, also known as CD169 and Sialoadhesin (Sn), is the first siglec family member identified. Siglec-1 is a 210 kDa type I single membrane spanning glycoprotein containing 17 immunoglobulin-like domains [1, 3]. Expression of Siglec-1 is found primarily on dendritic cells (DCs), macrophages and interferon induced monocytes [4–6]. The structure of Siglec-1 is unique among siglecs and its function as a receptor also is different compared to other receptors in this class, as it contains the most extracellular domains out of all the siglecs [7]. Sixteen of these extracellular domains are C2-set domains and the furthermost domain is the terminal V-set domain which contains the sialic acid binding pocket (Figure 2) [7]. The V-set domain of Siglec-1 is also highly conserved across vertebrate species, similar to Siglec-2 (CD22), Siglec-4 (MAG) and Siglec-15 [8]. Amino acid differences in the human and murine form of Siglec-2 necessitated the development of transgenic CD22 mice which expressed human CD22 [9].
Epigenetic regulation of T cell development
Published in International Reviews of Immunology, 2023
Avik Dutta, Harini Venkataganesh, Paul E. Love
Major histone epigenetic marks are methylation, acetylation and ubiquitination. Histone methyltransferases (HMT) catalyze the transfer of one, two, or three methyl groups to lysine (K = Lysine) or arginine (R = Arginine) residues of histone (H3 and H4) proteins [22]. There are three major types of histone methyltransferases, including SET domain containing (e.g. Setd1, Setd2, mixed lineage leukemia (MLL)1/2), non-SET domain containing (e.g. DOT1L) and arginine-specific (e.g. PRMT1) HMTs [22]. Trimethylation of lysine 9 of histone H3 [H3K9], lysine 27 [H3K27] or lysine 20 of Histone 4 [H4K20] are mainly found in heterochromatin and serve as transcriptional repressive marks [23]. On the other hand, H3K4, H3K36 and H3K79 are enriched in euchromatin and are usually associated with active transcription (Figure 1) [24].