TY - JOUR
T1 - Jarid2 is among a set of genes differentially regulated by Nkx2.5 during outflow tract morphogenesis
AU - Barth, Jeremy L.
AU - Clark, Christopher D.
AU - Fresco, Victor M.
AU - Knoll, Ellen P.
AU - Lee, Benjamin
AU - Argraves, W. Scott
AU - Lee, Kyu Ho
PY - 2010/7
Y1 - 2010/7
N2 - 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.
AB - 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.
KW - Chromatin immunoprecipitation
KW - Congenital heart disease
KW - Double outlet right ventricle
KW - Knockout
KW - Microarray
KW - Secondary heart field
UR - https://www.scopus.com/pages/publications/77953748302
UR - https://www.scopus.com/pages/publications/77953748302#tab=citedBy
U2 - 10.1002/dvdy.22341
DO - 10.1002/dvdy.22341
M3 - Article
C2 - 20549724
AN - SCOPUS:77953748302
SN - 1058-8388
VL - 239
SP - 2024
EP - 2033
JO - Developmental Dynamics
JF - Developmental Dynamics
IS - 7
ER -
