gene regulation
Dotaz
Zobrazit nápovědu
Cephalochordates, commonly known as amphioxus or lancelets, are the most basal subphylum of chordates. Cephalochordates are thus key to understanding the origin of vertebrates and molecular mechanisms underlying vertebrate evolution. The evolution of developmental control mechanisms during invertebrate-to-vertebrate transition involved not only gene duplication events, but also specific changes in spatial and temporal expression of many genes. To get insight into the spatiotemporal regulation of gene expression during invertebrate-to-vertebrate transition, functional studies of amphioxus gene regulatory elements are highly warranted. Here, we review transgenic studies performed in amphioxus and vertebrates using promoters and enhancers derived from the genome of Branchiostoma floridae. We describe the current methods of transgenesis in amphioxus, provide evidence of Tol2 transposon-generated transgenic embryos of Branchiostoma lanceolatum and discuss possible future directions. We envision that comparative transgenic analysis of gene regulatory sequences in the context of amphioxus and vertebrate embryos will likely provide an important mechanistic insight into the evolution of vertebrate body plan.
- Klíčová slova
- Chordates, Evolution, Gene regulation, Transgenic animal, Vertebrates,
- MeSH
- biologická evoluce MeSH
- geneticky modifikovaná zvířata MeSH
- kopinatci genetika fyziologie MeSH
- obratlovci genetika metabolismus MeSH
- regulace genové exprese fyziologie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Melanogenesis is a multistep biochemical process resulting in the formation of melanin in pigment cells in the skin and the eye. Three melanogenic factors, tyrosinase, TRP1, and TRP2 participate in the pathway. Here, the regulation of gene expression of these melanocyte-specific markers is shortly reviewed.
- MeSH
- genetická transkripce MeSH
- intramolekulární oxidoreduktasy * MeSH
- isomerasy genetika MeSH
- lidé MeSH
- melaniny biosyntéza genetika MeSH
- membránové glykoproteiny * MeSH
- oxidoreduktasy * MeSH
- proteiny genetika MeSH
- regulace genové exprese * MeSH
- tyrosinasa genetika MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- dopachrome isomerase MeSH Prohlížeč
- intramolekulární oxidoreduktasy * MeSH
- isomerasy MeSH
- melaniny MeSH
- membránové glykoproteiny * MeSH
- oxidoreduktasy * MeSH
- proteiny MeSH
- tyrosinasa MeSH
- tyrosinase-related protein-1 MeSH Prohlížeč
- TYRP1 protein, human MeSH Prohlížeč
The gut microbiome exhibits extreme compositional variation between hominid hosts. However, it is unclear how this variation impacts host physiology across species and whether this effect can be mediated through microbial regulation of host gene expression in interacting epithelial cells. Here, we characterize the transcriptional response of human colonic epithelial cells in vitro to live microbial communities extracted from humans, chimpanzees, gorillas, and orangutans. We find that most host genes exhibit a conserved response, whereby they respond similarly to the four hominid microbiomes. However, hundreds of host genes exhibit a divergent response, whereby they respond only to microbiomes from specific host species. Such genes are associated with intestinal diseases in humans, including inflammatory bowel disease and Crohn's disease. Last, we find that inflammation-associated microbial species regulate the expression of host genes previously associated with inflammatory bowel disease, suggesting health-related consequences for species-specific host-microbiome interactions across hominids.
- Klíčová slova
- Gut microbiome, Primates, Hominids, Gene regulation,
- MeSH
- Bacteria genetika MeSH
- druhová specificita MeSH
- epitelové buňky metabolismus MeSH
- exprese genu genetika MeSH
- feces mikrobiologie MeSH
- fylogeneze MeSH
- Gorilla gorilla mikrobiologie MeSH
- Hominidae genetika mikrobiologie MeSH
- idiopatické střevní záněty genetika MeSH
- lidé MeSH
- mikrobiota genetika MeSH
- Pan troglodytes mikrobiologie MeSH
- Pongo mikrobiologie MeSH
- regulace genové exprese genetika MeSH
- RNA ribozomální 16S genetika MeSH
- střevní mikroflóra genetika MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Názvy látek
- RNA ribozomální 16S MeSH
Sox3/SOX3 gene is considered to be one of the earliest neural markers in vertebrates. Despite the mounting evidence that Sox3/SOX3 is one of the key players in the development of the nervous system, limited data are available regarding the transcriptional regulation of its expression. This review is focused on the retinoic acid induced regulation of SOX3 gene expression, with particular emphasis on the involvement of retinoid receptors. Experiments with human embryonal carcinoma cells identified two response elements involved in retinoic acid/retinoid X receptor-dependent activation of the SOX3 gene expression: distal atypical retinoic acid-response element, consisting of two unique G-rich boxes separated by 49 bp, and proximal element comprising DR-3-like motif, composed of two imperfect hexameric half-sites. Importantly, the retinoic acid-induced SOX3 gene expression could be significantly down-regulated by a synthetic antagonist of retinoid receptors. This cell model provides a solid base for further studies on mechanism(s) underlying regulation of expression of SOX3 gene, which could improve the understanding of molecular signals that induce neurogenesis in the stem/progenitor cells both during development and in adulthood.
- MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- nervové kmenové buňky účinky léků metabolismus MeSH
- neurogeneze MeSH
- receptory kyseliny retinové účinky léků metabolismus MeSH
- responzivní elementy MeSH
- retinoidy farmakologie MeSH
- signální transdukce MeSH
- transkripční faktory SOXB1 genetika metabolismus MeSH
- vazebná místa MeSH
- vývojová regulace genové exprese * účinky léků MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- receptory kyseliny retinové MeSH
- retinoidy MeSH
- SOX3 protein, human MeSH Prohlížeč
- transkripční faktory SOXB1 MeSH
The organic cation transporter 1 (OCT1) is the dominant carrier of organic cationic drugs and some positively charged endogenous compounds into hepatocytes. OCT1 has unique expression pattern. It has the highest expression among drug transporters in normal human hepatocytes with large interindividual variability, but it has negligible expression in other tissues or their tumors. Nowadays, it is clear that the regulation of SLC22A1 gene encoding OCT1 transporter is rather complex and that transactivation with hepatocyte nuclear factor 4α (HNF4α) and CCAAT-enhancer-binding protein (C/EBPs) transcription factors as well as epigenetic regulation contribute to its unique hepatocyte-specific expression pattern. Unfortunately, species- and tissue-specific regulation of OCT1 and its orthologs as well as significant down-regulation in most immortalized cell lines hamper the study of SLC22A1 gene regulation. In the current review, we summarize our current understanding of human OCT1 transporter hepatic gene regulation and we propose potential post-transcriptional regulation by predicted miRNAs. We also discuss in detail recent findings on indirect regulation of the transporter via farnesoid X receptor (FXR), glucocorticoid receptor and pregnane X (PXR) receptor, which point out to potential novel mechanisms of xenobiotic-transporting and drug-metabolizing proteins regulation in the human liver as well as to potentially novel drug-drug interaction mechanisms. We also propose that comprehensive understanding of mechanisms of SLC22A1 gene regulation could direct research for other drug transporters and drug-metabolizing enzymes highly expressed in hepatocytes and controlled by HNF4α or other liver-enriched transcription factors.
- Klíčová slova
- Gene regulation, hepatic uptake, liver, nuclear receptors, organic cation transporter 1, transporter,
- MeSH
- epigeneze genetická MeSH
- hepatocytární jaderný faktor 4 metabolismus MeSH
- hepatocyty metabolismus MeSH
- lidé MeSH
- mikro RNA metabolismus MeSH
- pregnanový X receptor MeSH
- přenašeč organických kationtů 1 metabolismus MeSH
- proteiny vázající zesilovač transkripce CCAAT metabolismus MeSH
- receptory cytoplazmatické a nukleární metabolismus MeSH
- receptory glukokortikoidů metabolismus MeSH
- regulace genové exprese * MeSH
- steroidní receptory metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- farnesoid X-activated receptor MeSH Prohlížeč
- hepatocytární jaderný faktor 4 MeSH
- mikro RNA MeSH
- pregnanový X receptor MeSH
- přenašeč organických kationtů 1 MeSH
- proteiny vázající zesilovač transkripce CCAAT MeSH
- receptory cytoplazmatické a nukleární MeSH
- receptory glukokortikoidů MeSH
- steroidní receptory MeSH
Hybridization and polyploidization are important evolutionary processes whose impacts range from the alteration of gene expression and phenotypic variation to the triggering of asexual reproduction. We investigated fishes of the Cobitis taenia-elongatoides hybrid complex, which allowed us to disentangle the direct effects of both processes, due to the co-occurrence of parental species with their diploid and triploid hybrids. Employing morphological, ecological, and RNAseq approaches, we investigated the molecular determinants of hybrid and polyploid forms. In contrast with other studies, hybridization and polyploidy induced relatively very little transgressivity. Instead, Cobitis hybrids appeared intermediate with a clear effect of genomic dosing when triploids expressed higher similarity to the parent contributing two genome sets. This dosage effect was symmetric in the germline (oocyte gene expression), interestingly though, we observed an overall bias toward C. taenia in somatic tissues and traits. At the level of individual genes, expression-level dominance vastly prevailed over additivity or transgressivity. Also, trans-regulation of gene expression was less efficient in diploid hybrids than in triploids, where the expression modulation of homoeologs derived from the "haploid" parent was stronger than those derived from the "diploid" parent. Our findings suggest that the apparent intermediacy of hybrid phenotypes results from the combination of individual genes with dominant expression rather than from simple additivity. The efficiency of cross-talk between trans-regulatory elements further appears dosage dependent. Important effects of polyploidization may thus stem from changes in relative concentrations of trans-regulatory elements and their binding sites between hybridizing genomes. Links between gene regulation and asexuality are discussed.
- Klíčová slova
- asexuality, cis-/trans-regulation, expression-level dominance, hybridization, polyploidy, tissue-specific gene expression,
- MeSH
- ekosystém MeSH
- fenotyp MeSH
- hybridizace genetická * MeSH
- máloostní anatomie a histologie genetika metabolismus MeSH
- nepohlavní rozmnožování * MeSH
- polyploidie * MeSH
- regulace genové exprese * MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Vertebrates have greatly elaborated the basic chordate body plan and evolved highly distinctive genomes that have been sculpted by two whole-genome duplications. Here we sequence the genome of the Mediterranean amphioxus (Branchiostoma lanceolatum) and characterize DNA methylation, chromatin accessibility, histone modifications and transcriptomes across multiple developmental stages and adult tissues to investigate the evolution of the regulation of the chordate genome. Comparisons with vertebrates identify an intermediate stage in the evolution of differentially methylated enhancers, and a high conservation of gene expression and its cis-regulatory logic between amphioxus and vertebrates that occurs maximally at an earlier mid-embryonic phylotypic period. We analyse regulatory evolution after whole-genome duplications, and find that-in vertebrates-over 80% of broadly expressed gene families with multiple paralogues derived from whole-genome duplications have members that restricted their ancestral expression, and underwent specialization rather than subfunctionalization. Counter-intuitively, paralogues that restricted their expression increased the complexity of their regulatory landscapes. These data pave the way for a better understanding of the regulatory principles that underlie key vertebrate innovations.
- MeSH
- anotace sekvence MeSH
- genomika * MeSH
- kopinatci embryologie genetika MeSH
- lidé MeSH
- metylace DNA MeSH
- obratlovci genetika MeSH
- promotorové oblasti (genetika) MeSH
- regulace genové exprese * MeSH
- rozvržení tělního plánu genetika MeSH
- transkriptom genetika MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BCL3 is a putative proto-oncogene deregulated in haematopoieitic and solid tumours. It has been suggested that its oncogenic effects could be mediated, at least in part, by inducing proliferation and inhibiting cell death. To provide more insight into the mediators of these effects, we used an unbiased approach to analyse the mRNA expression changes after knocking-down BCL3 using specific shRNAs. One hundred eighty genes were up-regulated and sixtynine genes were down-regulated after knocking down BCL3. Function analyses showed enrichment in genes associated with cellular growth and proliferation, cell death and gene expression. We found that STAT3, an important oncogene in human cancer, was the central node of one of the most significant networks. We validated STAT3 as a bona fide target of BCL3 by additional interference RNA and in silico analyses of previously reported lymphoma patients.
- MeSH
- down regulace MeSH
- HeLa buňky MeSH
- lidé MeSH
- malá interferující RNA genetika metabolismus MeSH
- nádorové buněčné linie MeSH
- nádory děložního čípku genetika metabolismus MeSH
- protein bcl-3 MeSH
- proteiny genetika metabolismus MeSH
- protoonkogen Mas MeSH
- protoonkogenní proteiny genetika metabolismus MeSH
- regulace genové exprese u nádorů * MeSH
- RNA interference MeSH
- sekvenční analýza hybridizací s uspořádaným souborem oligonukleotidů MeSH
- stanovení celkové genové exprese MeSH
- transkripční faktor STAT3 genetika metabolismus MeSH
- transkripční faktory genetika metabolismus MeSH
- upregulace MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- BCL3 protein, human MeSH Prohlížeč
- malá interferující RNA MeSH
- MAS1 protein, human MeSH Prohlížeč
- protein bcl-3 MeSH
- proteiny MeSH
- protoonkogen Mas MeSH
- protoonkogenní proteiny MeSH
- transkripční faktor STAT3 MeSH
- transkripční faktory MeSH
DNA topoisomerases II regulate conformational changes in DNA topology. They act on double-stranded DNA, catalyzing its relaxation, decatenation and unknotting. Vertebrate cells express two isoforms of topoisomerase II, which are similar in structure, but different in function and regulation. Whereas the alpha isoform is indispensable for proper cell replication, the functions of the beta isoform as well as reasons for its evolution in vertebrates were long unclear. Unlike topoisomerase II alpha, the beta isoform is predominantly expressed in quiescent cells and has been implicated mainly in the process of gene transcription. Recently, new discoveries point on the role of the topoisomerase II beta in regulation of cellular differentiation and tissue development. Furthermore, contemporary discoveries are raising possibilities for novel therapeutic approaches involving selective targeting of either topoisomerase II isoform in potentiating antitumor and/or reducing adverse effects of topoisomerase II poisons.
- MeSH
- buněčná diferenciace fyziologie MeSH
- DNA vazebné proteiny fyziologie MeSH
- DNA-topoisomerasy typu II fyziologie MeSH
- lidé MeSH
- regulace genové exprese fyziologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- DNA vazebné proteiny MeSH
- DNA-topoisomerasy typu II MeSH
Paxillin (PXN) is a focal adhesion protein that has been implicated in signal transduction from the extracellular matrix. Recently, it has been shown to shuttle between the cytoplasm and the nucleus. When inside the nucleus, paxillin promotes cell proliferation. Here, we introduce paxillin as a transcriptional regulator of IGF2 and H19 genes. It does not affect the allelic expression of the two genes; rather, it regulates long-range chromosomal interactions between the IGF2 or H19 promoter and a shared distal enhancer on an active allele. Specifically, paxillin stimulates the interaction between the enhancer and the IGF2 promoter, thus activating IGF2 gene transcription, whereas it restrains the interaction between the enhancer and the H19 promoter, downregulating the H19 gene. We found that paxillin interacts with cohesin and the mediator complex, which have been shown to mediate long-range chromosomal looping. We propose that these interactions occur at the IGF2 and H19 gene cluster and are involved in the formation of loops between the IGF2 and H19 promoters and the enhancer, and thus the expression of the corresponding genes. These observations contribute to a mechanistic explanation of the role of paxillin in proliferation and fetal development.
- Klíčová slova
- Cohesin, Enhancer, H19, IGF2, Imprinting, Paxillin,
- MeSH
- buňky Hep G2 MeSH
- chromozomální proteiny, nehistonové genetika MeSH
- extracelulární matrix genetika MeSH
- fokální adheze genetika MeSH
- genomový imprinting genetika MeSH
- insulinu podobný růstový faktor II biosyntéza genetika MeSH
- koheziny MeSH
- lidé MeSH
- metylace DNA genetika MeSH
- paxilin aplikace a dávkování MeSH
- proliferace buněk účinky léků genetika MeSH
- promotorové oblasti (genetika) MeSH
- proteiny buněčného cyklu genetika MeSH
- RNA dlouhá nekódující biosyntéza genetika MeSH
- signální transdukce účinky léků MeSH
- vývoj plodu genetika MeSH
- vývojová regulace genové exprese MeSH
- zesilovače transkripce MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- chromozomální proteiny, nehistonové MeSH
- H19 long non-coding RNA MeSH Prohlížeč
- IGF2 protein, human MeSH Prohlížeč
- insulinu podobný růstový faktor II MeSH
- paxilin MeSH
- proteiny buněčného cyklu MeSH
- RNA dlouhá nekódující MeSH