NFIX

Nuclear factor 1 X-type is a protein that in humans is encoded by the NFIX gene.[5][6][7] NFI-X3, a splice variant of NFIX, regulates Glial fibrillary acidic protein and YKL-40 in astrocytes.[8]

NFIX
Identifiers
Aliases	NFIX, MRSHSS, NF1A, SOTOS2, nuclear factor I X, NF1-X, NF-I/X, CTF
External IDs	OMIM: 164005 MGI: 97311 HomoloGene: 1872 GeneCards: NFIX
Gene location (Human) Chr. Chromosome 19 (human)[1] Band 19p13.13 Start 12,995,608 bp[1] End 13,098,796 bp[1]
Gene location (Mouse) Chr. Chromosome 8 (mouse)[2] Band 8 C2|8 41.02 cM Start 84,699,876 bp[2] End 84,800,344 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • GO:0001131, GO:0001151, GO:0001130, GO:0001204 DNA-binding transcription factor activity • transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding • DNA binding • GO:0001948 protein binding • GO:0001200, GO:0001133, GO:0001201 DNA-binding transcription factor activity, RNA polymerase II-specific Cellular component • intracellular • cell nucleus Biological process • DNA replication • regulation of transcription, DNA-templated • negative regulation of transcription from RNA polymerase II promoter • transcription from RNA polymerase II promoter • transcription, DNA-templated • positive regulation of transcription from RNA polymerase II promoter Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	4784	18032
Ensembl	ENSG00000008441	ENSMUSG00000001911
UniProt	Q14938	P70257
RefSeq (mRNA)	NM_001271043 NM_001271044 NM_002501 NM_001365902 NM_001365982 NM_001365983 NM_001365984 NM_001365985 NM_001378404 NM_001378405	NM_001081981 NM_001081982 NM_001297601 NM_010906
RefSeq (protein)	NP_001257972 NP_001257973 NP_002492 NP_001352831 NP_001352911 NP_001352912 NP_001352913 NP_001352914 NP_001365333 NP_001365334	NP_001075450 NP_001075451 NP_001284530 NP_035036 NP_001357981 NP_001357982 NP_001357983 NP_001357984 NP_001357985 NP_001357986 NP_001357987 NP_001357988 NP_001357989 NP_001357990 NP_001357991 NP_001357992
Location (UCSC)	Chr 19: 13 – 13.1 Mb	Chr 8: 84.7 – 84.8 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Interactions

Nfix has been shown to interact with SKI protein[9] and it is also known to interact with AP-1.[8] NFI-X3 has been shown to interact with STAT3.[8]

In embryonic cells, Nfix has been shown to regulate intermediate progenitor cell (IPC) generation by promoting the transcription of the protein inscuteable (INSC). INSC regulates spindle orientation to facilitate the division of radial glia cells into IPC's. Nfix is thought to be necessary for the commitment of glia progeny into the intermediate progenitors. Mutations may cause overproduction of radial glia, impaired and improperly timed IPC development, and underproduction of neurons. [10]

In adult development, the timing of neural differentiation is regulated by Nfix to promote ongoing growth of the hippocampus and proper memory function. Nfix may suppress oligodendrocyte expression so cells remain committed to neuron development within the dentate gyrus. Intermediate progenitor cells can divide to produce neuroblasts. Neurons produced by Nfix null IPC's do not mature, usually die, and can contribute to cognitive impairments.[11]

Nfix interacts with myostatin and regulates temporal progression of muscle regeneration through modulation of myostatin expression. Nfix also inhibits slow-twith muscle phenotype.[12][13]

References

1. GRCh38: Ensembl release 89: ENSG00000008441 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000001911 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Seisenberger C, Winnacker EL, Scherthan H (Aug 1993). "Localisation of the human nuclear factor I/X (NFI/X) gene to chromosome 19p13 and detection of five other related loci at 1p21-22, 1q42-43, 5q15, 11p13 and 20q13 by FISH". Hum Genet. 91 (6): 535–537. doi:10.1007/bf00205076. PMID 8340106. S2CID 22365562.
6. Qian F, Kruse U, Lichter P, Sippel AE (Dec 1995). "Chromosomal localization of the four genes (NFIA, B, C, and X) for the human transcription factor nuclear factor I by FISH". Genomics. 28 (1): 66–73. doi:10.1006/geno.1995.1107. PMID 7590749.
7. "Entrez Gene: NFIX nuclear factor I/X (CCAAT-binding transcription factor)".
8. Singh SK, Bhardwaj R, Wilczynska KM, Dumur CI, Kordula T (November 2011). "A complex of nuclear factor I-X3 and STAT3 regulates astrocyte and glioma migration through the secreted glycoprotein YKL-40". J. Biol. Chem. 286 (46): 39893–39903. doi:10.1074/jbc.M111.257451. PMC 3220556. PMID 21953450.
9. Tarapore P, Richmond C, Zheng G, Cohen SB, Kelder B, Kopchick J, Kruse U, Sippel AE, Colmenares C, Stavnezer E (October 1997). "DNA binding and transcriptional activation by the Ski oncoprotein mediated by interaction with NFI". Nucleic Acids Res. 25 (19): 3895–3903. doi:10.1093/nar/25.19.3895. PMC 146989. PMID 9380514.
10. Harris, Lachlan; Zalucki, Oressia; Gobius, Ilan; McDonald, Hannah; Osinki, Jason; Harvey, Tracey J.; Essebier, Alexandra; Vidovic, Diana; Gladwyn-Ng, Ivan; Burne, Thomas H.; Heng, Julian I.; Richards, Linda J.; Gronostajski, Richard M.; Piper, Michael (2016-10-28). "Transcriptional Regulation of Intermediate Progenitor Cell Generation during Hippocampal Development". Development. 143: 4620–4630. doi:10.1242/dev.140681.
11. Harris, Lachlan; Zalucki, Oressia; Clément, Olivier; Fraser, James; Matuzelski, Elise; Oishi, Sabrina; Harvey, Tracey J.; Burne, Thomas H. J.; Heng, Julian I.; Richards, Linda J.; Gronostajski, Richard M.; Piper, Michael (2018-02-07). "Neurogenic Differentation by Hippocampal Neural Stem and Progenitor Cells is Biased by NFIX Expression". Development. 145: 1–12. doi:10.1242/dev.155689.
12. "Enhanced exercise and regenerative capacity in a mouse model that violates size constraints of oxidative muscle fibres | eLife".
13. "Nfix Regulates Temporal Progression of Muscle Regeneration through Modulation of Myostatin Expression: Cell Reports".

Further reading

• Apt D, Liu Y, Bernard HU (1994). "Cloning and functional analysis of spliced isoforms of human nuclear factor I-X: interference with transcriptional activation by NFI/CTF in a cell-type specific manner". Nucleic Acids Res. 22 (19): 3825–3833. doi:10.1093/nar/22.19.3825. PMC 308376. PMID 7937100.
• Sumner C, Shinohara T, Durham L, Traub R, Major EO, Amemiya K (1996). "Expression of multiple classes of the nuclear factor-1 family in the developing human brain: differential expression of two classes of NF-1 genes". J. Neurovirol. 2 (2): 87–100. doi:10.3109/13550289609146542. PMID 8799200.
• Wendler WM, Kremmer E, Förster R, Winnacker EL (1997). "Identification of pirin, a novel highly conserved nuclear protein". J. Biol. Chem. 272 (13): 8482–8489. doi:10.1074/jbc.272.13.8482. PMID 9079676.
• Liu Y, Bernard HU, Apt D (1997). "NFI-B3, a novel transcriptional repressor of the nuclear factor I family, is generated by alternative RNA processing". J. Biol. Chem. 272 (16): 10739–10745. doi:10.1074/jbc.272.16.10739. PMID 9099724.
• Tarapore P, Richmond C, Zheng G, Cohen SB, Kelder B, Kopchick J, Kruse U, Sippel AE, Colmenares C, Stavnezer E (1997). "DNA binding and transcriptional activation by the Ski oncoprotein mediated by interaction with NFI". Nucleic Acids Res. 25 (19): 3895–3903. doi:10.1093/nar/25.19.3895. PMC 146989. PMID 9380514.
• Müller K, Mermod N (2000). "The histone-interacting domain of nuclear factor I activates simian virus 40 DNA replication in vivo". J. Biol. Chem. 275 (3): 1645–1650. doi:10.1074/jbc.275.3.1645. PMID 10636857.
• Nakazato M, Chung HK, Ulianich L, Grassadonia A, Suzuki K, Kohn LD (2000). "Thyroglobulin repression of thyroid transcription factor 1 (TTF-1) gene expression is mediated by decreased DNA binding of nuclear factor I proteins which control constitutive TTF-1 expression". Mol. Cell. Biol. 20 (22): 8499–8512. doi:10.1128/MCB.20.22.8499-8512.2000. PMC 102156. PMID 11046146.
• Imagawa M, Sakaue R, Tanabe A, Osada S, Nishihara T (2000). "Two nuclear localization signals are required for nuclear translocation of nuclear factor 1-A". FEBS Lett. 484 (2): 118–124. doi:10.1016/S0014-5793(00)02119-0. PMID 11068044. S2CID 46556394.
• Norquay LD, Yang X, Sheppard P, Gregoire S, Dodd JG, Reith W, Cattini PA (2003). "RFX1 and NF-1 associate with P sequences of the human growth hormone locus in pituitary chromatin". Mol. Endocrinol. 17 (6): 1027–1038. doi:10.1210/me.2003-0025. PMID 12624117.
• Gopalan SM, Wilczynska KM, Konik BS, Bryan L, Kordula T (2006). "Nuclear factor-1-X regulates astrocyte-specific expression of the alpha1-antichymotrypsin and glial fibrillary acidic protein genes". J. Biol. Chem. 281 (19): 13126–13133. doi:10.1074/jbc.M601194200. PMID 16565071.
• Ravichandran V, Sabath BF, Jensen PN, Houff SA, Major EO (2006). "Interactions between c-Jun, nuclear factor 1, and JC virus promoter sequences: implications for viral tropism". J. Virol. 80 (21): 10506–10513. doi:10.1128/JVI.01355-06. PMC 1641797. PMID 16928756.

External links

• NFIX+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.