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Genetics and exercise: an introduction
Published in Adam P. Sharples, James P. Morton, Henning Wackerhage, Molecular Exercise Physiology, 2022
Claude Bouchard, Henning Wackerhage
A typical gene (Figure 3.8) consists of coding sequences termed exons (i.e. exons encode the amino acid sequence of a protein), interrupted by noncoding regions termed introns. Additionally, there are regulatory DNA sequences located upwards and downwards and at times far from the gene whose transcription depends on the regulatory DNA. The number of exons is highly variable, with a range from one (e.g. G-protein-coupled receptor genes, GPCRs, with no introns) to a few hundred exons, such as titin (gene symbol TTN), a gene with 363 exons.
Molecular Biology and Gene Therapy
Published in R James A England, Eamon Shamil, Rajeev Mathew, Manohar Bance, Pavol Surda, Jemy Jose, Omar Hilmi, Adam J Donne, Scott-Brown's Essential Otorhinolaryngology, 2022
A gene is a region of the chromosomal DNA that produces a functional ribonucleic acid molecule (RNA). It comprises regulatory DNA sequences that determine when and in which cell types that gene is expressed; exons are coding sequences and interspersed introns are non-coding DNA sequences.
Regulation of the Pituitary Gland by Dopamine
Published in Nira Ben-Jonathan, Dopamine, 2020
Each of the OT and AVP genes contains three exons and two introns. Both genes are located on the same chromosomal locus (chromosome 2 in mice and chromosome 20 in humans) but are transcribed in the opposite directions [8]. The domain which separates the OT and VP genes is relatively short and is called the “intergenic region” (IGR). The IGR in the rat and human is about 10–11 kbp in length, whereas that in the mouse is only 3.6 kbp. More than half of the rat IGR is represented by a long interspersed repeated DNA element that is completely missing in the mouse and human IGRs. The high sequence conservation found both upstream and downstream of these genes suggests that these domains contain regulatory DNA sequences.
Curcumin analog, GO-Y078, induces HO-1 transactivation-mediated apoptotic cell death of oral cancer cells by triggering MAPK pathways and AP-1 DNA-binding activity
Published in Expert Opinion on Therapeutic Targets, 2022
Ming-Hsien Chien, Pei-Chun Shih, Yi-Fang Ding, Li-Hsin Chen, Feng-Koo Hsieh, Meng-Ying Tsai, Pei-Yi Li, Chiao-Wen Lin, Shun-Fa Yang
It was reported that induction of HO-1 expression is mediated through cis-regulatory DNA sequences located in its promoter region. Several AP-1-binding sites were shown to be involved in the transcriptional induction of HO-1 by MAPKs and the polyphenol CUR or quercetin [53,54]. The AP-1 transcription factor is a dimer of Jun and Fos family proteins. In our study, we found that transcriptional activity of AP-1 was induced by GO-Y078 in OSCC cells. We actually observed that GO-Y078 treatment significantly increased the binding activities of c-Jun and c-Fos on the promoter region of the HMOX1 gene. These results suggest that GO-Y078 mediates transcriptional induction of HO-1 via targeting AP-1 in OSCC cells. In addition to AP-1, nuclear factor-erythroid 2-related factor 2 (Nrf2) is an another TF which can form a heterodimer with the small Maf protein and then bind to the antioxidant response element (ARE) of HMOX1 to regulate HO-1 expression. Actually, it was reported that HO-1 expression induced by CUR also requires activation of the Nrf2/ARE pathway [55]. In addition to transcriptional regulation of HMOX1 by CUR, epigenetic modulation is also involved in CUR-regulated HMOX1 expression through inhibiting histone deacetylase 2 (HDAC2) [40]. Whether the HDAC2 and Nrf2/ARE pathways are involved in GO-Y078-induced upregulation of HMOX1 in OSCC cells needs to be further investigated in the future.
CRX-linked macular dystrophy with intrafamilial variable expressivity
Published in Ophthalmic Genetics, 2018
Khaled Romdhane, Veronika Vaclavik, Daniel F. Schorderet, Francis L. Munier, H. Viet Tran
CRX is a 4-exon gene producing a 299-amino acid protein. It contains a paired–like homeodomain followed by a basic region; a WSP domain and a C-terminal OTX tail (1,4,13). Mutations that occur in the homeodomain are missense and those that occur in the last exon are premature termination codon or frameshifting (5). To date, more than 100 mutations in CRX have been reported (12). All mutations previously reported appeared to be dominant and 100% penetrant (13). Variable expressivity has also been described (5). In our family, the same mutation resulted in three different phenotypes, underlining this variable expressivity. On autofluorescence, while the father and uncle presented minimal changes, the proband showed a pattern evoking bull’s eye maculopathy as described in other cases of adult onset macular dystrophies caused by CRX mutation (5,6). With similar features of central hypoautofluorescence around a normal fluorescent fovea and surrounded by a rim of hyperautofluorescence in both eyes, he differs from those cases by extension of the lesion to the optic nerve head. Diffuse outer retinal atrophy with ONL thinning and disruption of the ellipsoid line was also described in other case reports (5,6), this clearly present in the proband but absent in the other family members. Only the thinning of the ONL was common between our three affected patients. Because the mutation is located in the last exon, the mutated transcript probably escapes nonsense-mediated mRNA decay, and a truncated protein is produced. This truncated protein would contain the paired homeobox domain necessary for binding of CRX to regulatory DNA sequences (v.g. promoters, enhancers), but would lack a large C-terminal region involved in protein interactions, containing namely the WSP, TTD1, TTD2 (transcriptional transactivation domains), and OTX-like domains. Potential mechanisms underlying the variable expressivity observed in this pedigree could therefore be increased expression of CRX from the wild-type allele compensating for the lacking transactivation function of the mutated one. Also, given the promiscuous binding of CRX and the closely related OTX family members to identical DNA regulatory motifs, OTX transcription factors may compensate to some extent for the lack of CRX transcriptional activity. Finally, binding of the truncated protein to DNA regulatory sequences through its functional paired-homeobox DNA binding domain may be sufficient to trigger some transcriptional activity from the mutated allele. As CRX binds to almost all photoreceptor cis-regulatory elements in a combinatorial way, polymorphisms in such elements could well be responsible for the heterogeneity of the phenotype described here and in other reports (14).