The aim of this study is to identify gene targets of TFII-I transcription factors involved in craniofacial development.
Design
Recent findings in individuals with Williams-Beuren syndrome who show facial dysmorphism and cognitive defects have pointed to TFII-I genes (GTF2I and GTF2IRD1) as the prime candidates responsible for these clinical features. However, TFII-I proteins are multifunctional transcriptional factors regulating a number of genes during development, and how their haploinsufficiency leads to the Williams-Beuren syndrome phenotype is currently unknown.
Results
Here we report the identification of three genes with a well-established relevance to craniofacial development as direct TFII-I targets. These genes, craniofacial development protein 1 (Cfdp1), Sec23 homolog A (Sec23a), and nuclear receptor binding SET domain protein 1 (Nsd1), contain consensus TFII-I binding sites in their proximal promoters; the chromatin immunoprecipitation analysis showed that TFII-I transcription factors are recruited to these sites in vivo.
Conclusions
The results suggest that transcriptional regulation of these genes by TFII-I proteins could provide a possible genotype-phenotype link in Williams-Beuren syndrome.
BayarsaihanD., RuddleF.H.Isolation and characterization of BEN, a member of the TFII-I family of DNA-binding proteins containing distinct helix-loop-helix domains. Proc Natl Acad Sci U S A.2000; 97: 7342–7347.
2.
BaujatG., RioM., RossignolS., SanlavilleD., LyonnetS., Le MerrerM., MunnichA., GicquelC., Cormier-DaireV., ColleauxL.Paradoxical NSD1 mutations in Beckwith-Wiedemann syndrome and 11p15 anomalies in Sotos syndrome. Am J Hum Genet.2004; 74: 715–720.
3.
BayarsaihanD., DunaiJ., GreallyJ.M., KawasakiK., SumiyamaK., EnkhmandakhB., ShimizuN., RuddleF.H.Genomic organization of the genes Gtf2ird1, Gtf2i, and Ncf1 at the mouse chromosome 5 region syntenic to the human chromosome 7q11.23 Williams syndrome critical region. Genomics.2002; 79: 137–143.
4.
BayésM., MaganoL.F., RiveraN., FloresR., Pérez JuradoL.A.Mutational mechanisms of Williams-Beuren syndrome deletions. Am J Hum Genet.2003; 73: 131–151.
5.
BoyadjievS.A., JusticeC.M., EyaidW., McKusickV.A., LachmanR.S., ChowdryA.B., JabakM., ZwaanJ., WilsonA.F., JabsE.W.A novel dysmorphic syndrome with open calvarial sutures and sutural cataracts maps to chromosome 14q13–q21. Hum Genet.2003; 113: 1–9.
6.
ChimgeN.O., MungunsukhO., RuddleF., BayarsaihanD.Expression profiling of BEN regulated genes in mouse embryonic fibroblasts. J Exp Zool.2007a; 308: 209–224.
7.
ChimgeN.O., MungunsukhO., RuddleF., BayarsaihanD.Gene expression analysis of TFII-I modulated genes in mouse embryonic fibroblasts. J Exp Zool.2007b; 308: 225–235.
8.
ChimgeN.O., MakeyevA.V., RuddleF.H., BayarsaihanD.Identification of the TFII-I family target genes in the vertebrate genome. Proc Natl Acad Sci U S A.2008; 106: 9006–9010.
9.
Crusselle-DavisV.J., ZhouZ., AnantharamanA., MoghimiB., DodevT., HuangS., BungertJ.Recruitment of coregulator complexes to the beta-globin gene locus by TFII-I and upstream stimulatory factor. FEES J.2007; 274: 6065–6073.
10.
DaiL., BellugiU., ChenX.N., Pulst-KorenbergA.M., Järvinen-PasleyA., Tirosh-WagnerT., EisP.S., GrahamJ., MillsD., SearcyY.. Is it Williams syndrome? GTF2IRD1 implicated in visual-spatial construction and GTF2I in sociability revealed by high resolution arrays. Am J Med Genet A.2009; 149: 302–314.
11.
DiekwischT.G.H., LuanX.CP27 function is necessary for cell survival and differentiation during tooth morphogenesis in organ culture. Gene.2002; 287: 141–147.
12.
DiekwischT.G.H., MarchesF., WilliamsA., LuanX.Cloning, gene expression, and characterization of CP27, a novel gene in mouse embryogenesis. Gene.1999; 235: 19–30.
13.
EnkhmandakhE., MakeyevA.V., ErdenechimegL., RuddleF.H., ChimgeN.O., Tussie-LunaM.I., RoyA., BayarsaihanD.Essential functions of the Williams-Beuren syndrome–associated TFII-I genes in embryonic development. Proc Natl Acad Sci U S A.2009; 106: 181–186.
14.
EraT., WitteO.N.Regulated expression of P210 Bcr-Abl during embryonic stem cell differentiation stimulates multipotential progenitor expansion and myeloid cell fate. Proc Natl Acad Sci U S A.2000; 97: 1737–1742.
15.
EwartA.K., MorrisC.A., AtkinsonD., JinW., SternesK., SpalloneP., StockA.D., LeppertM., KeatingM.T.Hemizygosity at the elastin locus in a developmental disorder, Williams syndrome. Nature Genet.1993; 5: 11–16.
16.
FranckeU.Williams-Beuren syndrome: genes and mechanisms. Hum Mol Genet.1999; 8: 1947–1954.
17.
GrimmT., WesselhoeftH.Zur Genetik des Williams-Beuren-Syndroms und der isolierten Form der supravalvulaeren Aortenstenose (Untersuchungen von 128 Familien). Z Kardiol.1980; 69: 168–172.
18.
HakimiM.A., DongY., LaneW.S., SpeicherD.W., ShiekhattarR.A candidate X-linked mental retardation gene is a component of a new family of histone deacetylase-containing complexes. J Biol Chem.2003; 278: 7234–7239.
19.
Järvinen-PasleyA., BellugiU., ReillyJ., MillsD.L., GalaburdaA., ReissA.L., KorenbergJ.R.Defining the social phenotype in Williams syndrome: a model for linking gene, the brain, and behavior. Dev Psychopathol.2008; 20: 1–35.
20.
JonesK.L., SmithD.W.The Williams elfin facies syndrome. A new perspective. J Pediatr.1975; 86: 718–723.
KuM., SokolS.Y., WuJ., Tussie-LunaM.I., RoyA.L., HataA.Positive and negative regulation of the transforming growth factor beta/activin target gene goosecoid by the TFII-I family of transcription factors. Mol Cell Biol.2005; 25: 7144–7157.
24.
LangM.R., LapierreL.A., FrotscherM., GoldenringJ.R., KnapikE.W.Secretory COPII coat component Sec23a is essential for craniofacial chondrocyte maturation. Nature Genet.2006; 38: 1198–1203.
25.
LeachK.M., VieiraK.F., KangS.H., AslanianA., TeichmannM., RoederR.G., BungertJ.Characterization of the human beta-globin downstream promoter region. Nucleic Acids Res.2003; 31: 1292–1301.
26.
LintonL.R., HarderL.D.Biology 315—Quantitative Biology Lecture Notes.Calgary, AB: University of Calgary;2007.
27.
LivakK.J., SchmittgenT.D.Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods.2001; 25: 402–408.
28.
LuanX., DiekwischT.G.CP27 affects viability, proliferation, attachment and gene expression in embryonic fibroblasts. Cell Prolif.2002; 35: 207–219.
29.
MariA., AmatiF., MingarelliR., GiannottiA., SebastioG., ColloridiV., NovelliG., DallapiccolaB.Analysis of the elastin gene in 60 patients with clinical diagnosis of Williams syndrome. Hum Genet.1995; 96: 444–448.
30.
MassE., BelostokyL.Craniofacial morphology of children with Williams syndrome. Cleft Palate Craniofac J.1993; 30: 343–349.
31.
MorrisC.A., MervisC.B.Williams syndrome and related disorders. Annu Rev Genomics Hum Genet.2000; 1: 461–484.
32.
NickersonE., GreenbergF., KeatingM.T., McCaskillC., ShafferL.G.Deletions of the elastin gene at 7q11.23 occur in approximately 90% of patients with Williams syndrome. Am J Hum Genet.1995; 56: 1156–1161.
33.
OhazamaA., SharpeP.T.TFII-I gene family during tooth development: candidate genes for tooth anomalies in Williams syndrome. Dev Dyn.2007; 236: 2884–2888.
34.
OsborneL.R.Williams-Beuren syndrome: unraveling the mysteries of a microdeletion disorder. Mol Genet Metab.1999; 67: 1–10.
35.
OsborneL.R., MartindaleD., SchererS.W., ShiX-M, HuizengaJ., HengH.H.Q., CostaT., PoberB., LewL., BrinkmanJ.. Identification of genes from a 500-kb region at 7q11.23 that is commonly deleted in Williams syndrome patients. Genomics.1996; 36: 328–336.
36.
Perez JuradoA.L.Williams-Beuren syndrome: a model of recurrent genomic mutation. Horm Res.2003; 1: 106–113.
37.
PollyP., HaddadiL.M., IssaL.L., SubramaniamN., PalmerS.J., TayE.S., HardemanE.C.hMusTRD1alpha1 represses MEF2 activation of the troponin I slow enhancer. J Biol Chem.2003; 278: 36603–36610.
38.
RajaiyaJ., NixonJ.C., AyersN., DesgrangesZ.P., RoyA.L., WebbC.F.Induction of immunoglobulin heavy-chain transcription through the transcription factor Bright requires TFII-I. Mol Cell Biol.2006; 26: 4758–4768.
39.
RingC., OgataS., MeekL., SongJ., OhtaT., MiyazonoK., ChoK.W.The role of a Williams-Beuren syndrome–associated helix-loop-helix domain–containing transcription factor in activin/nodal signaling. Genes Dev.2002; 16: 820–835.
40.
RoyA.L.Biochemistry and biology of the inducible multifunctional transcription factor TFII-I. Gene.2001; 274: 1–13.
41.
RoyA.L.Signal-induced functions of the transcription factor TFII-I. Biochim Biophys Acta.2007; 1769: 613–621.
42.
RoyA.L., DuH., GregorP.D., NovinaC.D., MartinezE., RoederR.G.Cloning of an inr- and E-box-binding protein, TFII-I, that interacts physically and functionally with USF1. EMBO J.1997; 16: 7091–7104.
TassabehjiM.Williams-Beuren syndrome: a challenge for genotype-phenotype correlations. Hum Mol Genet.2003; 12: 229–237.
45.
TassabehjiM., HammondP., Karmiloff-SmithA., ThompsonP., ThorgeirssonS.S., DurkinM.E., PopescuN.C., HuttonT., MetcalfeK., RuckaA.. GTF2IRD1 in craniofacial development of humans and mice. Science.2005; 310: 1184–1187.
46.
TurkmenS., Gillessen-KaesbachG., MeineckeP., AlbrechtB., NeumannL.M., HesseV., PalanduzS., BalgS., MajewskiF., FuchsS.. Mutations in NSD1 are responsible for Sotos syndrome, but are not a frequent finding in other overgrowth phenotypes. Eur J Hum Genet.2003; 11: 858–865.
47.
Tussie-LunaM.I., BayarsaihanD., SetoE., RuddleF.H., RoyA.L.Physical and functional interactions of histone deacetylase 3 with TFII-I family proteins and PIASxbeta. Proc Natl Acad Sci U S A.2002a; 99: 12807–12812.
48.
Tussie-LunaM.I., MichelB., HakreS., RoyA.L.The SUMO ubiquitin-protein isopeptide ligase family member Miz1/PIASxbeta /Siz2 is a transcriptional cofactor for TFII-I. J Biol Chem.2002b; 277: 43185–43193.
49.
UrbanZ., HelmsC., FeketeG., CsiszarK., BonnetD., MunnichA., Donis-KellerH., BoydC.D.7q11.23 deletions in Williams syndrome arise as a consequence of unequal meiotic crossover. Am J Hum Genet.1996; 59: 958–962.
50.
ValeroM.C., de LuisO., CrucesJ., Perez JuradoL.A.Fine-scale comparative mapping of the human 7q11.23 region and the orthologous region on mouse chromosome 5G: the low-copy repeats that flank the Williams-Beuren syndrome arose at breakpoint sites of an evolutionary inversion(s). Genomics.2000; 69: 1–13.
51.
VullhorstD., BuonannoA.Multiple GTF2I-like repeats of general transcription factor 3 exhibit DNA-binding properties: evidence for a common origin as a sequence-specific DNA interaction module. J Biol Chem.2005; 280: 31722–31731.
52.
WenY.D., CressW.D., RoyA.L., SetoE.Histone deacetylase 3 binds to and regulates the multifunctional transcription factor TFII-I. J Biol Chem.2003; 278: 1841–1847.
