NFIX explained

Nuclear factor 1 X-type is a protein that in humans is encoded by the NFIX gene.^{[1] [2] [3]} NFI-X3, a splice variant of NFIX, regulates Glial fibrillary acidic protein and YKL-40 in astrocytes.^[4]

Interactions

Nfix has been shown to interact with SKI protein^[5] and it is also known to interact with AP-1.^[4] NFI-X3 has been shown to interact with STAT3.^[4]

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. ^[6]

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.^[7]

Nfix interacts with myostatin and regulates temporal progression of muscle regeneration through modulation of myostatin expression. Nfix also inhibits the slow-twitch muscle phenotype.^{[8] [9]}

Further reading

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

Notes and References

1. Seisenberger C, Winnacker EL, Scherthan H . 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 . Human Genetics . 91 . 6 . 535–537 . July 1993 . 8340106 . 10.1007/bf00205076 . 22365562 .
2. Qian F, Kruse U, Lichter P, Sippel AE . 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 . July 1995 . 7590749 . 10.1006/geno.1995.1107 .
3. Web site: Entrez Gene: NFIX nuclear factor I/X (CCAAT-binding transcription factor).
4. Singh SK, Bhardwaj R, Wilczynska KM, Dumur CI, Kordula T . A complex of nuclear factor I-X3 and STAT3 regulates astrocyte and glioma migration through the secreted glycoprotein YKL-40 . The Journal of Biological Chemistry . 286 . 46 . 39893–39903 . November 2011 . 21953450 . 3220556 . 10.1074/jbc.M111.257451 . free .
5. Tarapore P, Richmond C, Zheng G, Cohen SB, Kelder B, Kopchick J, Kruse U, Sippel AE, Colmenares C, Stavnezer E . DNA binding and transcriptional activation by the Ski oncoprotein mediated by interaction with NFI . Nucleic Acids Research . 25 . 19 . 3895–3903 . October 1997 . 9380514 . 146989 . 10.1093/nar/25.19.3895 .
6. Harris L, Zalucki O, Gobius I, McDonald H, Osinki J, Harvey TJ, Essebier A, Vidovic D, Gladwyn-Ng I, Burne TH, Heng JI, Richards LJ, Gronostajski RM, Piper M . Transcriptional regulation of intermediate progenitor cell generation during hippocampal development . Development . 143 . 24 . 4620–4630 . December 2016 . 27965439 . 5201028 . 10.1242/dev.140681 . free .
7. Harris L, Zalucki O, Clément O, Fraser J, Matuzelski E, Oishi S, Harvey TJ, Burne TH, Heng JI, Gronostajski RM, Piper M . Neurogenic differentiation by hippocampal neural stem and progenitor cells is biased by NFIX expression . Development . 145 . 3 . 1–12 . February 2018 . 29437824 . 10.1242/dev.155689 . free .
8. Omairi S, Matsakas A, Degens H, Kretz O, Hansson KA, Solbrå AV, Bruusgaard JC, Joch B, Sartori R, Giallourou N, Mitchell R, Collins-Hooper H, Foster K, Pasternack A, Ritvos O, Sandri M, Narkar V, Swann JR, Huber TB, Patel K . Enhanced exercise and regenerative capacity in a mouse model that violates size constraints of oxidative muscle fibres . eLife . 5 . e16940 . August 2016 . 27494364 . 4975572 . 10.7554/eLife.16940 . Cossu G . free .
9. Rossi G, Antonini S, Bonfanti C, Monteverde S, Vezzali C, Tajbakhsh S, Cossu G, Messina G . Nfix Regulates Temporal Progression of Muscle Regeneration through Modulation of Myostatin Expression . Cell Reports . 14 . 9 . 2238–2249 . March 2016 . 26923583 . 4793149 . 10.1016/j.celrep.2016.02.014 .