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Role of Epigenetics in Immunity and Immune Response to Vaccination
Published in Mesut Karahan, Synthetic Peptide Vaccine Models, 2021
ncRNAs longer than 200 nt are classified as long ncRNAs. In a fashion similar to pre-miRNAs lncRNAs are also transcribed by RNA polymerase II and undergo 5′ capping and polyadenylation. The human genome encodes for approximately 16,000 lcnRNAs which give rise to almost 30,000 different transcripts. Despite being considered new additions to the field of RNA biology, the function of some lncRNAs has been known for almost 30 years. One of the lncRNAs whose function has been identified in the early 1990s is lncRNA Xist. Xist plays a central role in X-chromosome inactivation (Brown et al. 1992). Recent studies have demonstrated several new functions for lncRNAs including antiviral response in addition to regulation of development and differentiation (Fatica and Bozzoni 2014; Fortes and Morris 2016). A common mechanism for exerting such functions for lncRNAs is to act as post transcriptional regulators by altering mRNA/protein stability and translation (Yoon, Abdelmohsen, and Gorospe 2013).
Phosphoribosylpyrophosphate synthetase and its abnormalities
Published in William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop, Atlas of Inherited Metabolic Diseases, 2020
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop
The PRPS2 gene codes for a transcript in testis, a 318 amino acid sequence [22–24]. The PRPS1 gene is located between the α-galactosidase (GLA) and HPRT1 genes [14]. The PRPS1 and these two genes both undergo inactivation with Lyonization [25]. The PRPS2 gene is situated between two genes on the short arm that escape inactivation distally and ZFX proximally. The XIST gene is transcribed only from the inactive X chromosome. A third gene (PRPS3) maps to chromosome 7 and is expressed only in testis [22].
Epigenetic Reprogramming of Mammalian Primordial Germ Cells
Published in Cristina Camprubí, Joan Blanco, Epigenetics and Assisted Reproduction, 2018
Sebastian Canovas, Susana M. Chuva de Sousa Lopes
When the mouse embryo reaches the blastocyst stage (E3.5), the cells of the inner cell mass (ICM), express a combination of pluripotency genes (Pou5f1, Nanog, Sox2), that bind the Xist promoter/exon1 silencing it (70). In addition, POUF51 and ZFP42 (or REX1) upregulate the long non-coding Tsix, antisense of Xist. Subsequently Tsix and Xist dimerize forming a double-strand that is targeted for degradation via the RNAi machinery (71). Hence, Xist is downregulated and the silent X chromosome is reactivated. Half a day later (E4.0), each ICM cell undergoes X chromosome inactivation again, this time random X inactivation. Prior to implantation, mouse blastocysts are formed by ICM cells (with random X inactivation) and extraembryonic (trophectoderm and primitive endoderm) cells (with imprinted X inactivation). The Xi is transmitted to the daughter cells by mitosis and so the female embryo develops as mosaic, showing clonal expansion of cells with either a maternal or paternal Xi.
Variation in the expression level of MALAT1, MIAT and XIST lncRNAs in coronary artery disease patients with and without type 2 diabetes mellitus
Published in Archives of Physiology and Biochemistry, 2022
Nasim Sohrabifar, Sayyed Mohammad Hossein Ghaderian, Saeed Alipour Parsa, Hamid Ghaedi, Hossein Jafari
In the case of XIST lncRNA, it was stated higher expression of this lncRNA was seen in CAD patients who had verified T2DM compared to those without diabetes. According to the analysis of ROC results with an AUC of 0.79 in the second comparison group, the study of the increased expression of this XIST can be applied as a fair diagnostic marker for diabetic CAD patients. XIST can take a crucial part in the pathology of various diseases (Li et al.2013). Sathishkumar et al. showed that in comparison to control subjects the expression level of several lncRNAs, including XIST, in T2DM patients was significantly increased (Sathishkumar et al.2018). They suggested a role for XIST in T2DM progression through promoting insulin resistance and inflammation. To our knowledge, there is a lack of studies that have been specifically addressed the association between XIST expression and coronary artery disease. But, due to the well-known role of insulin resistance and inflammation in CAD pathogenesis (Anuurad et al.2009), XIST upregulation may have a role in diabetic CAD progression.
LncRNA XIST is involved in rheumatoid arthritis fibroblast-like synoviocytes by sponging miR-126-3p via the NF-κB pathway
Published in Autoimmunity, 2021
Wei Liu, Jing Song, Xingyu Feng, Haolong Yang, Wei Zhong
LncRNAs are universally transcribed in eukaryotic cells but have little or no protein coding function [35]. In recent years, the relationship between lncRNAs and the occurrence of complex diseases has received extensive attention [36]. XIST is a major regulatory gene for X chromosome inactivation in mammals, and the XIST gene can only be transcribed from the inactive X chromosome [17]. Studies have shown that XIST plays an important role in human cell differentiation, proliferation, and maintenance of genomic function and morphology [37,38]. However, the role and mechanism of XIST in RA are not clear. This study showed that the expression of XIST in synovial tissues and cells was significantly upregulated, suggesting that XIST may be related to the pathogenesis of RA. Knockdown of XIST could significantly reduce RA-FLS cell proliferation and increase RA-FLS cell apoptosis. In addition, down-regulation of XIST enhanced the expression levels of caspase-3 and Bax and decreased the expression levels of Bcl-2. Our findings revealed the important role of XIST in RA.
Sex differences in schizophrenia relevant to clinical care
Published in Expert Review of Neurotherapeutics, 2021
There are biological differences between all men and women, and the origin of this difference continues to be controversial. Arnold [9] proposed a general theory of sex difference in humans that rests on the fact that most females, at conception, possess two X chromosomes while most males have one X and one Y. There are some male-specific genes on the Y chromosome that females all lack, the main one being the testis-determining gene from which testes develop. In its absence, ovaries arise. Testes in men and ovaries in women secrete different levels of hormones (estrogens, androgens, progestins, and anti-Müllerian hormone) that subsequently exert an influence on most body organs, including, notably, the brain. The presence of two X chromosomes in females means that, in each cell, one of the two (either the maternal or the paternal X) has to be silenced in order to establish sexual equivalency of gene products. This process is called X chromosome inactivation, a mechanism for which the Xist gene is responsible. It encodes a long non-coding ribonucleic acid (RNA) sequence that is expressed only on the X chromosome that is destined for inactivation [10].