HGNC Approved Gene Symbol:GLIS1
Cytogenetic location:1p32.3 Genomic coordinates(GRCh38) :1:53,506,239-53,739,164 (from NCBI)
GLIS1 is a GLI (165220)-related Kruppel-like zinc finger protein that functions as an activator and repressor of transcription (Kim et al., 2002).
Using yeast 2-hybrid analysis with the ligand-binding domain of nuclear orphan receptor ROR-gamma (RORC; 602943) as bait,Kim et al. (2002) obtained a partial Glis1 cDNA from a mouse lymphoma cDNA library. Using this fragment to screen a mouse kidney cDNA library, followed by PCR and 5-prime RACE, they cloned full-length Glis1. The deduced 789-amino acid protein contains a bipartite nuclear localization signal, a proline-rich region, and a zinc finger domain consisting of 5 tandem C2H2-type zinc finger motifs. Northern blot analysis of mouse tissues detected highest expression of Glis1 in placenta and kidney, lower expression in testis, and little expression in other tissues examined. RT-PCR analysis detected high expression in kidney, low expression in brain, colon, brown fat, testis, and thymus, and no expression in lung, spleen, liver, pancreas, and muscle, In situ hybridization of mouse embryos showed that Glis1 was expressed primarily in the mesodermal lineages, including craniofacial regions, branchial arches, somites, vibrissal and hair follicles, limb buds, and myotomes. By confocal microscopy of monkey kidney fibroblast CV1 cells expressing full-length and mutant mouse Glis1,Kim et al. (2002) localized Glis1 to the nucleus in a speckled pattern similar to that observed for many transcription factors.
By EMSA analysis,Kim et al. (2002) showed that mouse Glis1 is able to bind oligonucleotides containing the Gli-binding site consensus sequence.
Using monohybrid and deletion analyses,Kim et al. (2002) showed that Glis1 contains a strong activation domain in the C terminus and a repressor domain in the N terminus. Glis1-mediated transactivation activity varied among different cell lines tested, andKim et al. (2002) suggested that these differences may be related to different levels of expression or activation of Glis1 coactivators. By cotransfection of Glis1 and CaMKiV (CAMK4;114080),Kim et al. (2002) showed that CAMK4 stimulates Glis1 transactivation activity.
By in situ hybridization analysis,Nakanishi et al. (2006) showed that Glis1 mRNA is not expressed in normal human epidermis or in normal mouse skin, but is highly induced in the epidermis of psoriatic patients and in PMA-treated mouse skin. GLIS1 expression was undetectable in human epidermal keratinocytes but increased significantly after treatment with proinflammatory agents PMA or interferon-gamma (IFNG;147570). PMA induction of GLIS1 expression was cell type-specific and confined to cell types in which PMA induction is accompanied by cell differentiation.Nakanishi et al. (2006) showed that in human keratinocytes immortalized by HPV-E6, full-length mouse Glis1 localized to the cytoplasm and a C-terminal truncated form of Glis1 that retains the zinc finger domain localized to the nucleus. By microarray analysis of a human epidermal keratinocyte cell line expressing the C-terminal truncated form of mouse Glis1,Nakanishi et al. (2006) found that Glis1 induced several genes known to be differentially regulated during epidermal differentiation, including S100A9 (123886), KLK7 (604438), SPRR/cornifin (SPRR1B;182266), involucrin (IVL;147360), and transglutaminase-1 (TGM1;190195).Nakanishi et al. (2006) suggested that Glis1 may play a role in the aberrant differentiation observed in psoriatic epidermis.
Maekawa et al. (2011) showed that Glis1 markedly enhances the generation of induced pluripotent stem cells (IPSCs) from both mouse and human fibroblasts when it is expressed together with Oct3/4 (164177), Sox2 (184429), and Klf4 (602253). Mouse IPSCs generated using this combination of transcription factors can form germline-competent chimeras. Glis1 is enriched in unfertilized oocytes and in embryos at the 1-cell stage. DNA microarray analyses show that Glis1 promotes multiple pro-reprogramming pathways, including Myc (190080), Nanog (607937), Lin28 (611043), Wnt (see606359), Esrrb (602167), and the mesenchymal-epithelial transition.Maekawa et al. (2011) concluded that Glis1 effectively promotes the direct reprogramming of somatic cells during iPSC generation.
The International Radiation Hybrid Mapping Consortium mapped the GLIS1 gene to chromosome 1 (SHGC-34268). By FISH,Kim et al. (2002) mapped the mouse Glis1 gene to chromosome 4C6.
Kim, Y.-S., Lewandoski, M., Perantoni, A. O., Kurebayashi, S., Nakanishi, G., Jetten, A. M.Identification of Glis1, a novel Gli-related, Kruppel-like zinc finger protein containing transactivation and repressor functions. J. Biol. Chem. 277: 30901-30913, 2002. [PubMed:12042312,related citations] [Full Text]
Maekawa, M., Yamaguchi, K., Nakamura, T., Shibukawa, R., Kodanaka, I., Ichisaka, T., Kawamura, Y., Mochizuki, H., Goshima, N., Yamanaka, S.Direct reprogramming of somatic cells is promoted by maternal transcription factor Glis1. Nature 474: 225-229, 2011. [PubMed:21654807,related citations] [Full Text]
Nakanishi, G., Kim, Y.-S., Nakajima, T., Jetten, A. M.Regulatory role for Kruppel-like zinc-finger protein Gli-similar 1 (Glis1) in PMA-treated and psoriatic epidermis J. Invest. Derm. 126: 49-60, 2006. [PubMed:16417217,images,related citations] [Full Text]
Alternative titles; symbols
HGNC Approved Gene Symbol: GLIS1
Cytogenetic location: 1p32.3 Genomic coordinates(GRCh38) : 1:53,506,239-53,739,164(from NCBI)
GLIS1 is a GLI (165220)-related Kruppel-like zinc finger protein that functions as an activator and repressor of transcription (Kim et al., 2002).
Using yeast 2-hybrid analysis with the ligand-binding domain of nuclear orphan receptor ROR-gamma (RORC; 602943) as bait, Kim et al. (2002) obtained a partial Glis1 cDNA from a mouse lymphoma cDNA library. Using this fragment to screen a mouse kidney cDNA library, followed by PCR and 5-prime RACE, they cloned full-length Glis1. The deduced 789-amino acid protein contains a bipartite nuclear localization signal, a proline-rich region, and a zinc finger domain consisting of 5 tandem C2H2-type zinc finger motifs. Northern blot analysis of mouse tissues detected highest expression of Glis1 in placenta and kidney, lower expression in testis, and little expression in other tissues examined. RT-PCR analysis detected high expression in kidney, low expression in brain, colon, brown fat, testis, and thymus, and no expression in lung, spleen, liver, pancreas, and muscle, In situ hybridization of mouse embryos showed that Glis1 was expressed primarily in the mesodermal lineages, including craniofacial regions, branchial arches, somites, vibrissal and hair follicles, limb buds, and myotomes. By confocal microscopy of monkey kidney fibroblast CV1 cells expressing full-length and mutant mouse Glis1, Kim et al. (2002) localized Glis1 to the nucleus in a speckled pattern similar to that observed for many transcription factors.
By EMSA analysis, Kim et al. (2002) showed that mouse Glis1 is able to bind oligonucleotides containing the Gli-binding site consensus sequence.
Using monohybrid and deletion analyses, Kim et al. (2002) showed that Glis1 contains a strong activation domain in the C terminus and a repressor domain in the N terminus. Glis1-mediated transactivation activity varied among different cell lines tested, and Kim et al. (2002) suggested that these differences may be related to different levels of expression or activation of Glis1 coactivators. By cotransfection of Glis1 and CaMKiV (CAMK4; 114080), Kim et al. (2002) showed that CAMK4 stimulates Glis1 transactivation activity.
By in situ hybridization analysis, Nakanishi et al. (2006) showed that Glis1 mRNA is not expressed in normal human epidermis or in normal mouse skin, but is highly induced in the epidermis of psoriatic patients and in PMA-treated mouse skin. GLIS1 expression was undetectable in human epidermal keratinocytes but increased significantly after treatment with proinflammatory agents PMA or interferon-gamma (IFNG; 147570). PMA induction of GLIS1 expression was cell type-specific and confined to cell types in which PMA induction is accompanied by cell differentiation. Nakanishi et al. (2006) showed that in human keratinocytes immortalized by HPV-E6, full-length mouse Glis1 localized to the cytoplasm and a C-terminal truncated form of Glis1 that retains the zinc finger domain localized to the nucleus. By microarray analysis of a human epidermal keratinocyte cell line expressing the C-terminal truncated form of mouse Glis1, Nakanishi et al. (2006) found that Glis1 induced several genes known to be differentially regulated during epidermal differentiation, including S100A9 (123886), KLK7 (604438), SPRR/cornifin (SPRR1B; 182266), involucrin (IVL; 147360), and transglutaminase-1 (TGM1; 190195). Nakanishi et al. (2006) suggested that Glis1 may play a role in the aberrant differentiation observed in psoriatic epidermis.
Maekawa et al. (2011) showed that Glis1 markedly enhances the generation of induced pluripotent stem cells (IPSCs) from both mouse and human fibroblasts when it is expressed together with Oct3/4 (164177), Sox2 (184429), and Klf4 (602253). Mouse IPSCs generated using this combination of transcription factors can form germline-competent chimeras. Glis1 is enriched in unfertilized oocytes and in embryos at the 1-cell stage. DNA microarray analyses show that Glis1 promotes multiple pro-reprogramming pathways, including Myc (190080), Nanog (607937), Lin28 (611043), Wnt (see 606359), Esrrb (602167), and the mesenchymal-epithelial transition. Maekawa et al. (2011) concluded that Glis1 effectively promotes the direct reprogramming of somatic cells during iPSC generation.
The International Radiation Hybrid Mapping Consortium mapped the GLIS1 gene to chromosome 1 (SHGC-34268). By FISH, Kim et al. (2002) mapped the mouse Glis1 gene to chromosome 4C6.
Kim, Y.-S., Lewandoski, M., Perantoni, A. O., Kurebayashi, S., Nakanishi, G., Jetten, A. M.Identification of Glis1, a novel Gli-related, Kruppel-like zinc finger protein containing transactivation and repressor functions. J. Biol. Chem. 277: 30901-30913, 2002. [PubMed: 12042312] [Full Text: https://doi.org/10.1074/jbc.M203563200]
Maekawa, M., Yamaguchi, K., Nakamura, T., Shibukawa, R., Kodanaka, I., Ichisaka, T., Kawamura, Y., Mochizuki, H., Goshima, N., Yamanaka, S.Direct reprogramming of somatic cells is promoted by maternal transcription factor Glis1. Nature 474: 225-229, 2011. [PubMed: 21654807] [Full Text: https://doi.org/10.1038/nature10106]
Nakanishi, G., Kim, Y.-S., Nakajima, T., Jetten, A. M.Regulatory role for Kruppel-like zinc-finger protein Gli-similar 1 (Glis1) in PMA-treated and psoriatic epidermis J. Invest. Derm. 126: 49-60, 2006. [PubMed: 16417217] [Full Text: https://doi.org/10.1038/sj.jid.5700018]
Dear OMIM User,
To ensure long-term funding for the OMIM project, we have diversified our revenue stream. We are determined to keep this website freely accessible. Unfortunately, it is not free to produce. Expert curators review the literature and organize it to facilitate your work. Over 90% of the OMIM's operating expenses go to salary support for MD and PhD science writers and biocurators. Please join your colleagues by making a donation now and again in the future. Donations are an important component of our efforts to ensure long-term funding to provide you the information that you need at your fingertips.
Thank you in advance for your generous support,
Ada Hamosh, MD, MPH
Scientific Director, OMIM