View source for Biology:Myelin regulatory factor

{{Short description|Mammalian protein found in Homo sapiens}}
{{Infobox gene}}
{{Pfam_box
| Symbol = MYRF
| Name = Myelin regulatory factor
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| caption = 
| InterPro= IPR026933
| SMART=
| PROSITE = 
| SCOP = 
| TCDB =
| OPM family=
| OPM protein=
| Pfam= 
| PDB=
| Membranome superfamily= 237
}}

'''Myelin regulatory factor''' ([https://www.ncbi.nlm.nih.gov/pubmed/22956843 MyRF]), also known as '''myelin gene regulatory factor''' (MRF), is a [[Biology:Protein|protein]] that in humans is encoded by the ''MYRF'' [[Biology:Gene|gene]].

== Orthologs ==

Myelin regulatory factor is encoded by the ''Myrf/GM98'' gene in mice and by the ''MYRF'' gene in humans.<ref>{{cite web | title = MYRF | url = https://www.uniprot.org/uniprot/Q9Y2G1 | publisher = Universal Protein Resource (UniProt) Consortium | access-date = 2012-06-13 }}</ref> The family of MyRF-like-proteins also contains the orthologues pqn-47 from ''[[Biology:Caenorhabditis elegans|C. elegans]]'' and MYRFA from ''[[Biology:Dictyostelium|Dictyostelium]]''.<ref name="pmid22811266">{{cite journal |vauthors=Senoo H, Wang HY, Araki T, Williams JG, Fukuzawa M | title = An orthologue of the Myelin-gene Regulatory Transcription Factor regulates Dictyostelium prestalk differentiation | journal = Int. J. Dev. Biol. | volume = 56 | issue = 5 | pages = 325–32 | year = 2012 | pmid = 22811266 | doi = 10.1387/ijdb.120030jw | pmc=3586673}}</ref>  All orthologs have a [[Biology:DNA-binding domain|DNA-binding domain]] of high homology to the ''[[Biology:Saccharomyces cerevisiae|Saccharomyces cerevisiae]]'' protein Ndt80 (a [[Biology:P53|p53]]-like [[Biology:Transcription factor|transcription factor]]) and therefore likely act as a transcription factor.

== Function ==

MyRF is a [[Biology:Transcription factor|transcription factor]] that promotes the expression of many genes important in the production of [[Biology:Myelin|myelin]].<ref name="Koenning_2012">{{cite journal |vauthors=Bujalka H, Koenning M, Jackson S, Perreau VM, Pope B, Hay CM, Mitew S, Hill AF, Lu QR, Wegner M, Srinivasan R, Svaren J, Willingham M, Barres BA, Emery B | title = MYRF Is a Membrane-Associated Transcription Factor That Autoproteolytically Cleaves to Directly Activate Myelin Genes | journal = PLOS Biol | volume = 11 | issue = 8 | pages = e1001625 |date=September 2013 | pmid = 23966833| pmc = 3742440 | doi = 10.1371/journal.pbio.1001625 | doi-access = free }}</ref> It is therefore of critical importance in the development and maintenance of myelin sheaths.<ref name="pmid22956843">{{cite journal |vauthors=Koenning M, Jackson S, Hay CM, Faux C, Kilpatrick TJ, Willingham M, Emery B | title = Myelin gene regulatory factor is required for maintenance of myelin and mature oligodendrocyte identity in the adult CNS | journal = J. Neurosci. | volume = 32 | issue = 36 | pages = 12528–42 |date=September 2012 | pmid = 22956843 | doi = 10.1523/JNEUROSCI.1069-12.2012 | pmc = 3752083 }}</ref>

The expression of MYRF is specific to mature, myelinating oligodendrocytes in the [[Biology:Central nervous system|CNS]].<ref name="Emery_2009">{{cite journal |vauthors=Emery B, Agalliu D, Cahoy JD, Watkins TA, Dugas JC, Mulinyawe SB, Ibrahim A, Ligon KL, Rowitch DH, Barres BA | title = Myelin gene regulatory factor is a critical transcriptional regulator required for CNS myelination | journal = Cell | volume = 138 | issue = 1 | pages = 172–85 |date=July 2009 | pmid = 19596243 | pmc = 2757090 | doi = 10.1016/j.cell.2009.04.031 }}</ref><ref name="pmid18171944">{{cite journal |vauthors=Cahoy JD, Emery B, Kaushal A, Foo LC, Zamanian JL, Christopherson KS, Xing Y, Lubischer JL, Krieg PA, Krupenko SA, Thompson WJ, Barres BA | title = A transcriptome database for astrocytes, neurons, and oligodendrocytes: a new resource for understanding brain development and function | journal = J. Neurosci. | volume = 28 | issue = 1 | pages = 264–78 |date=January 2008 | pmid = 18171944 | doi = 10.1523/JNEUROSCI.4178-07.2008 | pmc = 6671143 }}</ref>  It has been shown to be critical for the maintenance of myelin by these cells. Following [[Physics:Ablation|ablation]] of MYRF the expression of myelin genes such as PLP1, [[Biology:Myelin basic protein|MBP]], [[Biology:Myelin-associated glycoprotein|MAG]] and [[Biology:Myelin oligodendrocyte glycoprotein|MOG]] drops rapidly.<ref name="pmid22956843" /> Therefore, MYRF is a key regulator and likely a direct activator of the expression of these genes.<ref name="Koenning_2012"/>

== Animal models ==

Mice that lose MYRF during adulthood present with a severe demyelination similar to that seen in animal models of multiple sclerosis. This underlines the importance of an active renewal of proteins in the myelin sheath. Further, the activity of MYRF increases during remyelination, suggesting it has a critical role in this process.<ref name="pmid22956843" /> Animals with repressed Myrf in a proportion of oligodendrocyte precursor cells showed a delayed functional recovery from spinal cord injury.<ref>{{cite conference |vauthors=Duncan GJ, Plemel JR, Hilton BJ, Liu J, Kramer JK, Kim J, Mao S, Tetzlaff W | title = Myelin gene regulatory factor knockout delays functional recovery from spinal cord injury | conference = Neuroscience 2012 |date= October 2012 | pages = S60 | url = http://ep65.eventpilotadmin.com/web/page.php?page=IntHtml&project=SfN12&id=24750 }}</ref>

Myrf has been shown to be significantly downregulated in a mouse model carrying the same mutation in the [[Biology:NPC1|NPC1]] protein that is underlying Niemann-Pick type C1 disease, a neurodegenerative process in which dysmyelination is a main pathogenic factor. Therefore, a disruption of oligodendrocyte formation and myelination may be the root cause of the neurological abnormalities.<ref name="pmid21938520">{{cite journal |vauthors=Yan X, Lukas J, Witt M, Wree A, Hübner R, Frech M, Köhling R, Rolfs A, Luo J | title = Decreased expression of myelin gene regulatory factor in Niemann-Pick type C 1 mouse | journal = Metab Brain Dis | volume = 26 | issue = 4 | pages = 299–306 |date=December 2011 | pmid = 21938520 | doi = 10.1007/s11011-011-9263-9 | s2cid = 26878522 }}</ref>

== References ==
{{Reflist|35em}}

{{Transcription factors|g4}}

[[Category:Transcription factors]]

{{Sourceattribution|Myelin regulatory factor}}