The transcription factor PRDM16 regulates differentiation of brown adipocyte tissue in mice. Recently, however, it has been demonstrated that genetic knockout of Prdm16 in mice leads to a complete cleft of the secondary palate in offspring. To identify genes whose promoters bind PRDM16 in mouse embryonic palate/maxillary mesenchymal cells, we have conducted a chromatin immunoprecipitation-promoter microarray analysis (ChIP-Chip). One hundred and twenty-two gene promoters were identified as capable of binding PRDM16. These could be functionally grouped to include those on genes linked to muscle development, chondrogenesis and osteogenesis, in addition to many transcription factors. These results suggest that PRDM16 may play a role in differentiation of mesenchymal cells in the embryonic secondary palate that contribute to the anterior, bony palate and posterior, muscular palate.
MochizukiN, ShimizuS, NagasawaT, TanakaH, TaniwakiM, YokotaJ, MorishitaK. A novel gene, MEL1, mapped to 1p36.3 is highly homologous to the MDS1/EVI1 gene and is transcriptionally activated in t(1;3)(p36;q21)-positive leukemia cells. Blood2000;96:3209–14
2.
NishikataI, SasakiH, IgaM, TatenoY, ImayoshiS, AsouN, NakamuraT, MorishitaK. A novel EVI1 gene family, MEL1, lacking a PR domain (MEL1S) is expressed mainly in t(1;3)(p36;q21)-positive AML and blocks G-CSF-induced myeloid differentiation. Blood2003;102:3323–32
3.
KajimuraS, SealeP, KubotaK, LunsfordE, FrangioniJV, GygiSP, SpiegelmanBM. Initiation of myoblast to brown fat switch by a PRDM16-C/EBP-beta transcriptional complex. Nature2009;460:1154–8
HornKH, WarnerDR, PisanoM, GreeneRM. PRDM16 expression in the developing mouse embryo. Acta Histochem2011;113:150–5
6.
SealeP, KajimuraS, YangW, ChinS, RohasLM, UldryM, TavernierG, LanginD, SpiegelmanBM. Transcriptional control of brown fat determination by PRDM16. Cell Metab2007;6:38–54
7.
WarnerDR, HornKH, MuddL, WebbCL, GreeneRM, PisanoMM. PRDM16/MEL1: a novel Smad binding protein expressed in murine embryonic orofacial tissue. Biochim Biophys Acta2007;1773:814–20
8.
BjorkBC, Turbe-DoanA, PrysakM, HerronBJ, BeierDR. Prdm16 is required for normal palatogenesis in mice. Hum Mol Genet2010;19:774–89
9.
ItoY, YeoJY, ChytilA, HanJ, BringasPJ, NakajimaA, ShulerCF, MosesHL, ChaiY. Conditional inactivation of Tgfbr2 in cranial neural crest causes cleft palate and calvaria defects. Development2003;130:5269–80
10.
LivakKJ, SchmittgenTD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods2001;25:402–8
11.
PisanoMM, GreeneRM. Epidermal growth factor potentiates the induction of ornithine decarboxylase activity by prostaglandins in embryonic palate mesenchymal cells: effects on cell proliferation and glycosaminoglycan synthesis. Dev Biol1987;122:419–31
12.
JohnsonWE, LiW, MeyerCA, GottardoR, CarrollJS, BrownM, LiuXS. Model-based analysis of tiling-arrays for ChIP-chip. Proc Natl Acad Sci USA2006;103:12457–62
13.
KajimuraS, SealeP, TomaruT, Erdjument-BromageH, CooperMP, RuasJL, ChinS, TempstP, LazarMA, SpiegelmanBM. Regulation of the brown and white fat gene programs through a PRDM16/CtBP transcriptional complex. Genes Dev2008;22:1397–409
14.
HuangDW, ShermanBT, LempickiRA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc2009;4:44–57
15.
ChenJ, ShapiroHS, SodekJ. Development expression of bone sialoprotein mRNA in rat mineralized connective tissues. J Bone Miner Res1992;7:987–97
16.
MukhopadhyayP, GreeneRM, ZachariasW, WeinrichMC, SinghS, YoungWWJr, PisanoMM. Developmental gene expression profiling of mammalian, fetal orofacial tissue. Birth Defects Res A Clin Mol Teratol2004;70:912–26
17.
McDaneldTG, HannonK, MoodyDE. Ankyrin repeat and SOCS box protein 15 regulates protein synthesis in skeletal muscle. Am J Physiol Regul Integr Comp Physiol2006;290:R1672–82
18.
McDaneldTG, SpurlockDM. Ankyrin repeat and suppressor of cytokine signaling (SOCS) box-containing protein (ASB) 15 alters differentiation of mouse C2C12 myoblasts and phosphorylation of mitogen-activated protein kinase and Akt. J Anim Sci2008;86:2897–902
19.
CharrasseS, ComunaleF, FortierM, Portales-CasamarE, DebantA, Gauthier-RouviereC. M-cadherin activates Rac1 GTPase through the Rho-GEF trio during myoblast fusion. Mol Biol Cell2007;18:1734–43
20.
GuzzoRM, WigleJ, SalihM, MooreED, TuanaBS. Regulated expression and temporal induction of the tail-anchored sarcolemmal-membrane-associated protein is critical for myoblast fusion. Biochem J2004;381:599–608
JakobsenLP, BorupR, VestergaardJ, LarsenLA, LageK, MarounLL, KjaerI, NiemannCU, AndersenM, KnudsenMA, MollgardK, TommerupN. Expression analyses of human cleft palate tissue suggest a role for osteopontin and immune related factors in palatal development. Exp Mol Med2009;41:77–85
23.
DaviesSJ, WiseC, VenkateshB, MirzaG, JeffersonA, VolpiEV, RagoussisJ. Mapping of three translocation breakpoints associated with orofacial clefting within 6p24 and identification of new transcripts within the region. Cytogenet Genome Res2004;105:47–53
24.
MertesF, Martinez-MoralesJR, NoldenT, SporleR, WittbrodtJ, LehrachH, HimmelbauerH. Cloning of mouse ojoplano, a reticular cytoplasmic protein expressed during embryonic development. Gene Expr Patterns2009;9:562–7
