Abstract
FSHD region gene 1 (FRG1), as the name suggests, is the primary candidate gene for fascioscapulohumeral muscular dystrophy disease. It seemingly affects muscle physiology in normal individuals but in FSHD, where it is found to be highly upregulated, might be involved in disruption of face, scapula and humeral skeletal muscle. Literature on FRG1, reviewed from 1996 to 2016, reveals that it is primarily associated with muscle development and maintenance. Approximately 75% of FSHD patients also show vascular abnormalities indicating that FRG1 might have some part to play in these abnormalities. Research involving vasculature in X. laevis larvae shows that FRG1 positively affects normal vasculature. Few of the well-established angiogenic regulators seem to get affected by abnormal expression level of FRG1. Its primary localization in sub nuclear structures like Cajal bodies and nuclear speckles indicates regulation of the above-mentioned factors by transcriptional and post-transcriptional machineries, but in-depth studies need to be done to conclude a clear statement. In this review, we have attempted to present all the work done on FRG1, all the lacunas which need to be unraveled, and hypothesized a model for our readers to get an insight into its molecular mechanism.
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References
Adams JC 2004 Roles of fascin in cell adhesion and motility. Curr. Opin. Cell Biol. 16 590–596
Altschul SF, Gish W, Miller W, Myers EW and Lipman DJ 1990 Basic local alignment search tool. J. Mol. Biol. 215 403–410
Arnould S, Delenda C, Grizot S, Desseaux C, Paques F, Silva GH and Smith J 2011 The I-CreI meganuclease and its engineered derivatives: applications from cell modification to gene therapy. Protein Eng. Des. Sel. 24 27–31
Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN and Bourne PE 2000 The protein data bank. Nucleic Acids Res. 28 235–242
Chen SC, Frett E, Marx J, Bosnakovski D, Reed X, Kyba M and Kennedy BK 2011 Decreased proliferation kinetics of mouse myoblasts overexpressing FRG1. PloS One 6 e19780
Chevalier BS and Stoddard BL 2001 Homing endonucleases: structural and functional insight into the catalysts of intron/intein mobility. Nucleic Acids Res. 29 3757–3774
Clark LN, Koehler U, Ward DC, Wienberg J and Hewitt JE 1996 Analysis of the organisation and localisation of the FSHD-associated tandem array in primates: implications for the origin and evolution of the 3.3 kb repeat family. Chromosoma 105 180–189
Cross MJ and Claesson-Welsh L 2001 FGF and VEGF function in angiogenesis: signalling pathways, biological responses and therapeutic inhibition. Trends Pharmacol. Sci. 22 201–207
Edwards RA and Bryan J 1995 Fascins, a family of actin bundling proteins. Cell Motil. Cytoskeleton 32 1–9
Feeney SJ, McGrath MJ, Sriratana A, Gehrig SM, Lynch GS, D’Arcy CE, Price JT, McLean CA, et al. 2015 FHL1 reduces dystrophy in transgenic mice overexpressing FSHD muscular dystrophy region gene 1 (FRG1). PLoS One 10 e0117665
Ferri G, Huichalaf CH, Caccia R and Gabellini D 2015 Direct interplay between two candidate genes in FSHD muscular dystrophy. Hum. Mol. Genet. 24 1256–1266
Flower DR 1996 The lipocalin protein family: structure and function. Biochem. J. 318 1–14
Gabellini D, Green MR and Tupler R 2002 Inappropriate gene activation in FSHD: a repressor complex binds a chromosomal repeat deleted in dystrophic muscle. Cell 110 339–348
Gabellini D, D'Antona G, Moggio M, Prelle A, Zecca C, Adami R, Angeletti B, Ciscato P, et al. 2006 Facioscapulohumeral muscular dystrophy in mice overexpressing FRG1. Nature 439 973–977
Gabriels J, Beckers MC, Ding H, Vriese DA, Plaisance S, Maarel VSM, Padberg GW, Frants RR, et al. 1999 Nucleotide sequence of the partially deleted D4Z4 locus in a patient with FSHD identifies a putative gene within each 3.3 kb element. Gene 236 25–32
Geng LN, Yao Z, Snider L, Fong AP, Cech JN, Young JM, van der Maarel SM, Ruzzo WL, et al. 2012 DUX4 activates germline genes, retroelements, and immune mediators: implications for facioscapulohumeral dystrophy. Dev. Cell 22 38–51
Grewal PK, Todd LC, van der Maarel S, Frants RR and Hewitt JE 1998 FRG1, a gene in the FSH muscular dystrophy region on human chromosome 4q35, is highly conserved in vertebrates and invertebrates. Gene 216 13–19
Grewal PK, van Geel M, Frants RR, de Jong P and Hewitt JE 1999 Recent amplification of the human FRG1 gene during primate evolution. Gene 227 79–88
Hanel ML, Wuebbles RD and Jones PL 2009 Muscular dystrophy candidate gene FRG1 is critical for muscle development. Dev. Dyn. 238 1502–1512
Hanel ML, Sun C-YJ, Jones TI, Long SW, Zanotti S, Milner D and Jones PL 2011 Facioscapulohumeral muscular dystrophy (FSHD) region gene 1 (FRG1) is a dynamic nuclear and sarcomeric protein. Differentiation. 81 107–118
Kim SK, Lund J, Kiraly M, Duke K, Jiang M, Stuart JM, Eizinger A, Wylie BN, et al. 2001 A gene expression map for Caenorhabditis elegans. Science 293 2087–2092
Koningsbruggen VS, Dirks RW, Mommaas AM, Onderwater JJ, Deidda G, Padberg GW, Frants RR and Maarel VSM 2004 FRG1P is localised in the nucleolus, Cajal bodies, and speckles. J. Med. Gen. 41
Koningsbruggen S, Straasheijm KR, Sterrenburg E, Graaf N, Dauwerse HG, Frants RR and Maarel SM 2007 FRG1P-mediated aggregation of proteins involved in pre-mRNA processing. Chromosoma 116 53–64
Korc M and Friesel RE 2009 The role of fibroblast growth factors in tumor growth. Curr. Cancer Drug Targets. 9 639–651
Kureishy N, Sapountzi V, Prag S, Anilkumar N and Adams JC 2002 Fascins, and their roles in cell structure and function. BioEssays 24 350–361
Lecroisey C, Ségalat L and Gieseler K 2007 The C. elegans dense body: anchoring and signaling structure of the muscle. J. Muscle Res. Cell Motil. 28 79–87
Liu Q, Jones TI, Tang VW, Brieher WM and Jones PL 2010 Facioscapulohumeral muscular dystrophy region gene-1 (FRG-1) is an actin-bundling protein associated with muscle-attachment sites. J. Cell Sci. 123 1116–1123
Lunt PW 1998 44th ENMC international workshop: facioscapulohumeral muscular dystrophy: molecular studies 19-21 July 1996, Naarden, The Netherlands. Neuromuscul. Disord. 8 126–130
Moerman DG and Williams BD 2006 Sarcomere assembly in C. elegans muscle. WormBook
Nahabedian JF, Qadota H, Stirman JN, Lu H and Benian GM 2012 Bending amplitude - a new quantitative assay of C. elegans locomotion: identification of phenotypes for mutants in genes encoding muscle focal adhesion components. Methods 56 95–102
Neguembor MV, Xynos A, Onorati MC, Caccia R, Bortolanza S, Godio C, Pistoni M, Corona DF, et al. 2013 FSHD muscular dystrophy region gene 1 binds Suv4-20h1 histone methyltransferase and impairs myogenesis. J. Mol. Cell Biol. 5 294–307
Olwin BB, Arthur K, Hannon K, Hein P, McFall A, Riley B, Szebenyi G, Zhou Z, et al. 1994 Role of FGFs in skeletal muscle and limb development. Mol. Reprod. Dev. 39 90–91
Ori M, Nardini M, Casini P, Perris R and Nardi I 2006 XHas2 activity is required during somitogenesis and precursor cell migration in Xenopus development. Development 133 631–640
Osborne RJ, Welle S, Venance SL, Thornton CA and Tawil R 2007 Expression profile of FSHD supports a link between retinal vasculopathy and muscular dystrophy. Neurology 68 569–577
Padberg GW, Brouwer OF and Keizer RJW 1995 On the significance of retinal vascular disease and hearing loss in facioscapulohumeral muscular dystrophy. Muscle Nerve Suppl. 2 S73–S80
Rappsilber J, Ryder U, Lamond AI and Mann M 2002 Large-scale proteomic analysis of the human spliceosome. Genome Res. 12 1231–1245
Saito K, Kigawa T and Yokoyama S Riken Structural Genomics/Proteomics initiative. Solution structure of mouse FRG1 protein.PDB ID: 2YUG
Sancisi V, Germinario E, Esposito A, Morini E, Peron S, Moggio M, Tomelleri G, Danieli-Betto D, et al. 2014 Altered Tnnt3 characterizes selective weakness of fast fibers in mice overexpressing FSHD region gene 1 (FRG1). Am. J. Phys. 306 R124–R137
Sun C-YJY, van Koningsbruggen S, Long SW, Straasheijm K, Klooster R, Jones TI, Bellini M, Levesque L, et al. 2011 Facioscapulohumeral muscular dystrophy region gene 1 is a dynamic RNA-associated and actin-bundling protein. J. Mol. Biol. 411 397–416
van Deutekom JC, Lemmers RJ, Grewal PK, van Geel M, Romberg S, Dauwerse HG, Wright TJ, Padberg GW, et al. 1996 Identification of the first gene (FRG1) from the FSHD region on human chromosome 4q35. Hum. Mol. Genet. 5 581–590
Wallace LM, Garwick-Coppens SE, Tupler R and Harper SQ 2011 RNA interference improves myopathic phenotypes in mice over-expressing FSHD region gene 1 (FRG1). Mol. Ther. 19 2048–2054
Wuebbles RD, Hanel ML and Jones PL 2009 FSHD region gene 1 (FRG1) is crucial for angiogenesis linking FRG1 to facioscapulohumeral muscular dystrophy-associated vasculopathy. Dis. Model. Mech. 2 267–274
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[Hansda AK, Tiwari A and Dixit M 2017 Current status and future prospect of FSHD region gene 1. J. Biosci.]
Arman Kunwar Hansda and Ankit Tiwari contributed equally to this work.
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Hansda, A.K., Tiwari, A. & Dixit, M. Current status and future prospect of FSHD region gene 1. J Biosci 42, 345–353 (2017). https://doi.org/10.1007/s12038-017-9681-x
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DOI: https://doi.org/10.1007/s12038-017-9681-x