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
Further, GFI1 retroviral overexpression in cells of Th2 led to an increase in the rate of cellular survival and proliferation [77]. During the infection or in vitro stimulation with parasites, including Schistosoma mansoni and helminth parasite, T cells that lack of GFI1 failed to generate IL-4 optimally [80]. Mechanistically, GFI1 works to inhibit GATA3 proteasomal degradation by targeting its SNAG domain at the N-terminal position [78]. As cellular differentiation of Th2 cells is getting impaired in the case of G9a-deficient Th2 cells, it may increase the chances of interactions between these three G9a/GFI1/GATA3 critical for transcriptional module establishment, which leads to type 11 cytokine locus activation [15]. As per G9a’s role, the N-terminus of ligand activating receptors present on the nuclear hormone regulate gene expression to act as a scaffold [35]. Based on the above available results, it is very clear that in T cells, G9a N-terminus might aid in GATA3, GFI1, and the various other factors that potentially play a role in optimal Th2-cell development. In the cellular differentiation of Treg cells and Th17 cells, involvement of GFI1 has also been observed [81].
Secreted effectors of the innate mucosal barrier
Published in Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald, Principles of Mucosal Immunology, 2020
Michael A. McGuckin, Andre J. Ouellette, Gary D. Wu
Notch signaling, which controls cell fate decisions in many different tissues, also determines secretory (goblet, enteroendocrine, tuft and Paneth cells) versus absorptive cell lineage development in the intestinal epithelium (Figure 4.3). Activation of one of four Notch receptors by any one of several ligands, from either the Delta or Jagged/Serrate families, results in the proteolytic cleavage and liberation of the Notch intracellular domain from the plasma membrane by γ-secretase. The Notch intracellular domain subsequently translocates into the nucleus where it forms a transcriptional activation complex with RBP-jk (also known as CSL), displacing histone deacetylase corepressors and recruiting histone acetyltransferases, leading to transcriptional activation of Notch target genes such as hairy/enhancer of split (HES). HES1, a basic helix-loop-helix (bHLH) transcriptional repressor, inhibits the expression of another bHLH factor, ATOH1 (Math1 for mouse, Hath1 for human), suppressing secretory cell lineage differentiation in the intestinal epithelium and leading to disproportionate numbers of absorptive enterocytes. The intestinal epithelium of Math1 knockout mice is populated only by absorptive enterocytes. By contrast, the inhibition of Notch signaling by CSL gene knockout, or with γ-secretase inhibitors, induces Math1 expression, leading to the conversion of all epithelial cells into goblet cells. HES1 knockout mice, although embryonic lethal, show an increase in goblet, enteroendocrine, and Paneth cells, with decreased numbers of absorptive enterocytes. Likely downstream of Math1 is the zinc finger transcriptional repressor, Gfi1, which is involved in the generation of Paneth and goblet, but not enteroendocrine, cells. Interestingly, the loss of Kruppel-like factor 4 (Klf4), a zinc finger transcription factor that is repressed by Notch signaling, leads to reduced goblet cell numbers.
Analysis of core mutation and TET2/ASXL1 mutations DNA methylation profile in myelodysplastic syndrome
Published in Hematology, 2023
Yue Feng, Haiping Liang, Xingchun Luo, Yu Zhu, Bei Liu, Meining Han
The top 10 hub genes of hypomethylated DMGs included AR, CACNA1C, PBX1, HPGDS, GFI1, CPE, RBFOX3, DLX2, PARP1 and SPIB. PBX1 has been shown to play a role in oncogenesis by regulating multiple biological processes, including proliferation, invasion, metastasis and angiogenesis [43], and it is associated with myeloid leukaemia [44]. GFI1 is a transcription factor with essential roles in controlling the differentiation of myeloid and lymphoid cells [45]. Studies have suggested associations of GFI1 expression levels with the prediction of survival outcomes and response to treatment of patients with AML, MDS and MM [46–48]. PARP1 is a proto-oncogene that encodes a DNA-dependent poly (ADP-ribosyl) transferase associated with DNA repair, transcription, cell proliferation and apoptosis. PARP1 is known to play critical roles in DNA damage detection and repair [49]. PARP1 was reported to be a novel therapeutic target in patients with AML and MDS [50].
Pediatric embryonal brain tumors in the molecular era
Published in Expert Review of Molecular Diagnostics, 2020
Bryan K. Li, Salma Al-Karmi, Annie Huang, Eric Bouffet
This group is transcriptionally characterized by GABAnergic and photoreceptor pathway activation. They are considered copy number-driven tumors, as only rare somatic nucleotide variants including mutations of SMARCA4, CTDNEP1, MLL2 have been reported [12]. Amplification of MYC is seen in 10–20% of cases, frequently as a gene fusion with PVT1 secondary to complex rearrangements of chr 8q24. Broad chromosomal arm level-changes are common, notably isochromosome 17q (i17q), seen in 40% of cases. Aberrant enhancer associated GFI1 activation related to focal alterations of chr 1 and 9 are seen among 20% of cases [43]. Recent proteomic studies have revealed a subset of group 3 tumors are characterized by MYC activation through either gene amplification or interestingly, an increase in post-translational modification of MYC that altered its half-life and transcriptional activity [19]. Preclinical data from targeting this pathway using BET/bromodomain inhibitors, which target MYC and MYCN-associated transcription activity, have shown promise [51,52].