Jarid2 is among a set of genes differentially regulated by Nkx2.5 during outflow tract morphogenesis.
Nkx2.5, a transcription factor implicated in human congenital heart disease, is required for regulation of second heart field (SHF) progenitors contributing to outflow tract (OFT). Here, we define a set of genes (Lrrn1, Elovl2, Safb, Slc39a6, Khdrbs1, Hoxb4, Fez1, Ccdc117, Jarid2, Nrcam, and Enpp3) expressed in SHF containing pharyngeal arch tissue whose regulation is dependent on Nkx2.5. Further investigation shows that Jarid2, which has been implicated in OFT morphogenesis, is a direct target of Nkx2.5 regulation. Jarid2 expression was up-regulated in SHF mesoderm of Nkx2.5-deficient embryos. Chromatin immunoprecipitation analysis showed Nkx2.5 interaction with consensus binding sites in the Jarid2 promoter in pharyngeal arch cells. Finally, Jarid2 promoter activity and mRNA expression levels were down-regulated by Nkx2.5 overexpression. Given the role of Jarid2 as a regulator of early cardiac proliferation, these findings highlight Jarid2 as one of several potential mediators of the critical role played by Nkx2.5 during OFT morphogenesis.
Barth
Jeremy L
JL
Regenerative Medicine and Cell Biology Department, Medical University of South Carolina,173 Ashley Avenue, Charleston, SC 29425, USA.
Clark
Christopher D
CD
Fresco
Victor M
VM
Knoll
Ellen P
EP
Lee
Benjamin
B
Argraves
W Scott
WS
Lee
Kyu-Ho
KH
D000818:Animals; D001665:Binding Sites; D001934:Branchial Region / Q000196:embryology / Q000378:metabolism; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D004707:Endoderm / Q000378:metabolism; D006321:Heart / Q000196:embryology*; D006352:Heart Ventricles / Q000196:embryology / Q000378:metabolism; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D017403:In Situ Hybridization; D008648:Mesoderm / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D063151:Polycomb Repressive Complex 2; D011401:Promoter Regions, Genetic / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; C093650:Jarid2 protein, mouse; D009419:Nerve Tissue Proteins; C484469:Nkx2-5 protein, mouse; D014157:Transcription Factors; D063151:Polycomb Repressive Complex 2