ZNF proteiini GLIS1 (1p32.3) reprogrammoi ja edistää MET- suuntaa

ZNF perhe GLIS

7.6.2019

Suomennosta M.Cassandrin artikkelista (2017)

GLIS1 on C2H2-tyyppinen Krüppelin kaltainen sinkkisormiproteiini, joka osallistuu psoriasiksen patogeneesiin. GLIS1 mRNA ilmenee vain psoriaattisen ihon suprabasaalisessa epidermiksessä, muta normaali-ihossa sitä ei ilmene. Tämä tieto voisi viitata siihen,että LIS1 osallistuu psoriaattisessa epidemiksessä epänormaalin erilaistumisen säätelyyn. Mikroarray- analyysit ovat johdonmukaissti osoittaneet, että GLIS1 säätelee transkriptionaalisesti useiden sellaisten geenien ilmentymistä, jotka osallistuvat epidermaalisten keratinosyyttien säätelyyn, kuten S100A9, KLK7, SPRR ( pienet proliinipitoiset proteiinit, small proline rich proteins), involukriini (IVL, involucrin) ja transglutaminaasi 1(TGM1).

GLIS1 omaa rakenteessaan vaimennusdomeenin (repressor domain) N-terminaalissaan ja aktivaatiodomeenin C-terminaalissaan ja saattaa johtaa sekä vaimentavaan että transaktivoivaan funktioon.

GLIS1 säätelee kohdegeeniensä transkriptiota sitoutumalla oligonukleotideihin, jotka sisältävät GLIS1:tä sitovan konsensussekvenssin GACCACCCAC, kuten elektroforeettiset mobility-shift-menetelmät osoittavat.

Lisäksi tiedetään, että alkiokehityksen aikana GLIS1 ilmenee ajallisesti ja tilavuudellisesti vaihtelevin mallein säädellen täten geeni-ilmenemää kehitysprosessin eri vaiheissa, kuten alkiolla tehdyt in situ hybridisointimenetelmät ovat osoittaneet. “

Lisäteitoa PubMed geeni-hausta. Näyttää olevan uudelleenohjelmoiva geeni ja edistää mesenkymaalisesta epiteliaaliseen trnsitiot (MET) ja indusoituu hypoxiasta ei-kanonisesti.

GLIS1 (1p32.3) (GLI-similar 1)

https://www.ncbi.nlm.nih.gov/gene/148979

Summary GLIS1 is a GLI (MIM 165220)-related Kruppel-like zinc finger protein that functions as an activator and repressor of transcription (Kim et al., 2002 [PubMed 12042312]).[supplied by OMIM, Mar 2008] Expression Low expression observed in reference dataset See more

Preferred Names: zinc finger protein GLIS1

Names: GLI-similar 1

Conserved Domains (3) summary

COG5048
Location:260 → 339

COG5048; FOG: Zn-finger [General function prediction only]

sd00017
Location:264 → 286

ZF_C2H2; C2H2 Zn finger [structural motif]

pfam13465
Location:278 → 305

zf-H2C2_2; Zinc-finger double domain

Related articles in PubMed

1. The Krüppel-like zinc finger transcription factor, GLI-similar 1, is regulated by hypoxia-inducible factors via non-canonical mechanisms. Khalesi E, et al. Biochem Biophys Res Commun, 2013 Nov 15. PMID 24383088
2. GLIS1 rs797906: an increased risk factor for late-onset Parkinson's disease in the Han Chinese population. Song W, et al. Eur Neurol, 2012. PMID 22759478
3. Regulatory role for Krüppel-like zinc-finger protein Gli-similar 1 (Glis1) in PMA-treated and psoriatic epidermis. Nakanishi G, et al. J Invest Dermatol, 2006 Jan. PMID 16417217, Free PMC Article
4. Direct reprogramming of somatic cells is promoted by maternal transcription factor Glis1. Maekawa M, et al. Nature, 2011 Jun 8. PMID 21654807 Glis1 is enriched in unfertilized oocytes and in embryos at the one-cell stage. DNA microarray analyses show that Glis1 promotes multiple pro-reprogramming pathways, including Myc, Nanog, Lin28, Wnt, Essrb and the mesenchymal-epithelial transition (MET). These results therefore show that Glis1 effectively promotes the direct reprogramming of somatic cells during iPSC generation.
5. Identification of Glis1, a novel Gli-related, Kruppel-like zinc finger protein containing transactivation and repressor functions. Kim YS, et al. J Biol Chem, 2002 Aug 23. PMID 12042312

See all (15) citations in PubMed

GeneRIFs: Gene References Into Functions

1. These results suggest that the hypoxic signaling pathway may play a pivotal role in regulating the reprogramming factor GLIS1, via non-canonical mechanisms involving partner transcription factor rather than by direct HIF transactivation. GLI-similar 1 (GLIS1) is important for the reprogramming of fibroblasts into induced pluripotent stem cells (iPSCs). However, the molecular mechanisms of regulation of GLIS1 expression remain unclear. We have therefore examined GLIS1 expression in various cancer cell lines and demonstrated that GLIS1 expression was dramatically increased under hypoxic conditions. Importantly, GLIS1 expression was significantly attenuated in VHL-overexpressing renal cell carcinoma cells compared to the VHL-deficient parent control. Moreover, promoter analysis demonstrated that GLIS1 transcription was regulated by hypoxia through a hypoxia-inducible factors (HIFs)-dependent mechanism. Co-transfection experiments revealed that HIF-2α had greater potency on the GLIS1 promoter activation than HIF-1α. Subsequent studies using wild-type and mutant HIF-2α demonstrated that DNA binding activity was not necessary but TADs were critical for GLIS1 induction. Finally, co-transfection experiments indicated that HIF-2α cooperated with AP-1 family members in upregulating GLIS1 transcription. These results suggest that the hypoxic signaling pathway may play a pivotal role in regulating the reprogramming factor GLIS1, via non-canonical mechanisms involving partner transcription factor rather than by direct HIF transactivation.
2. found that allele 'A' of rs797906 SNP increases the risk for late-onset Parkinson Disease in the Han Chinese population.
3. results therefore show that Glis1 effectively promotes the direct reprogramming of somatic cells during iPSC generation.
4. Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
5. Transcriptional factor Glis1 is involved in the regulation of aberrant differentiation observed in psoriatic epidermis.