GLIS1
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| Location (UCSC) | Chr 1: 53.51 – 53.74 Mb | Chr 4: 107.29 – 107.49 Mb | |||||||
| PubMed search | [3] | [4] | |||||||
| View/Edit Human | View/Edit Mouse |
Glis1 (Glis Family Zinc Finger 1) is gene encoding a
Structure
Glis1 is an 84.3 kDa proline rich protein composed of 789 amino acids.[6] No crystal structure has yet been determined for Glis1, however it is homologous to other proteins in many parts of its amino acid sequence whose structures have been solved.
Zinc finger domain
Glis1 uses a
Termini
Glis1 has an activation domain at its C-terminus and a repressive domain at its N-terminus. The repressive domain is much stronger than the activation domain meaning transcription is weak. The activation domain of Glis1 is four times stronger in the presence of CaM kinase IV. This may be due to a coactivator. A proline-rich region of the protein is also found towards the N-terminal. The protein's termini are fairly unusual, and have no strong sequence similarity other proteins.[6]
Use in cell reprogramming
Glis1 can be used as one of the four factors used in reprogramming somatic cells to induced pluripotent stem cells.[7] The three transcription factors Oct3/4, Sox2 and Klf4 are essential for reprogramming but are extremely inefficient on their own, fully reprogramming roughly only 0.005% of the number of cells treated with the factors.[11] When Glis1 is introduced with these three factors, the efficiency of reprogramming is massively increased, producing many more fully reprogrammed cells. The transcription factor c-Myc can also be used as the fourth factor and was the original fourth factor used by Shinya Yamanaka who received the 2012 Nobel Prize in Physiology or Medicine for his work in the conversion of somatic cells to iPS cells.[12][13][14] Yamanaka's work allows a way of bypassing the controversy surrounding stem cells.[14]
Mechanism
Somatic cells are most often fully differentiated in order to perform a specific function, and therefore only express the genes required to perform their function. This means the genes that are required for differentiation to other types of cell are packaged within chromatin structures, so that they are not expressed.[15]
Glis1 reprograms cells by promoting multiple pro-reprogramming pathways.
The result of the various changes in gene expression is the conversion of
Advantages over c-myc
Glis1 has a number of extremely important advantages over c-myc in cell reprogramming.
- No risk of cancer: Although c-myc enhances the efficiency of reprogramming, its major disadvantage is that it is a cancer development.[7]
- Production of fewer 'bad' colonies: While c-myc promotes the proliferation of reprogrammed cells, it also promotes the proliferation of 'bad' cells which have not reprogrammed properly and make up the vast majority of cells in a dish of treated cells. Glis1 actively suppresses the proliferation of cells that have not fully reprogrammed, making the selection and harvesting of the properly reprogrammed cells less laborious.[7][19] This is likely to be due to many of these 'bad' cells expressing Glis1 but not all four of the reprogramming factors. When expressed on its own, Glis1 inhibits proliferation.[7]
- More efficient reprogramming: The use of Glis1 reportedly produces more fully reprogrammed iPS cells than c-myc. This is an important quality given the inefficiency of reprogramming.[7]
Disadvantages
- Inhibition of Proliferation: Failure to stop Glis1 expression after reprogramming inhibits cell proliferation and ultimately leads to the death of the reprogrammed cell. Therefore, careful regulation of Glis1 expression is required.[20] This explains why Glis1 expression is switched off in embryos after they have started to divide.[7][20]
Roles in disease
Glis1 has been implicated to play a part in a number of diseases and disorders.
Psoriasis
Glis1 has been shown to be heavily up regulated in
Late onset Parkinson's Disease
A certain allele of Glis1 which exists due to a
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000174332 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000034762 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Entrez Gene: GLIS family zinc finger 1".
- ^ PMID 12042312.
- ^ S2CID 4428172.*Lay summary in: Tiu G (June 9, 2011). "Stem Cell Pioneer Yamanaka Discovers New Factor, Glis1, For iPS Cell Production". AsianScientist.
- PMID 20865670.
- ^ PMID 8378770.
- ^ S2CID 24135293.
- S2CID 1705950.
- S2CID 1565219.
- S2CID 8531539.
- ^ a b "The Nobel Prize in Physiology or Medicine – 2012 Press Release". Nobel Media AB. 8 October 2012.
- ^ Ralston A, Shaw K (2008). "Gene Expression Regulates Cell Differentiation". Nature Education. 1 (1).
- PMID 19779035.
- S2CID 28899778.
- ^ PMID 22722606.
- ^ S2CID 459050.
- ^ S2CID 22317543.
- PMID 16417217.
- S2CID 5823615.
- PMID 12107827.
- PMID 22653731.
- S2CID 25891959.