TY - JOUR
T1 - Neural crest specification and migration independently require nsd3-related lysine methyltransferase activity
AU - Jacques-Fricke, Bridget T.
AU - Gammill, Laura S.
PY - 2014/12/15
Y1 - 2014/12/15
N2 - Neural crest precursors express genes that cause them to become migratory, multipotent cells, distinguishing them from adjacent stationary neural progenitors in the neurepithelium. Histone methylation spatiotemporally regulates neural crest gene expression; however, the protein methyltransferases active in neural crest precursors are unknown. Moreover, the regulation of methylation during the dynamic process of neural crest migration is unclear. Here we show that the lysine methyltransferase NSD3 is abundantly and specifically expressed in premigratory and migratory neural crest cells. NSD3 expression commences before up-regulation of neural crest genes, and NSD3 is necessary for expression of the neural plate border gene Msx1, as well as the key neural crest transcription factors Sox10, Snail2, Sox9, and FoxD3, but not gene expression generally. Nevertheless, only Sox10 his tone H3 lysine 36 dimethylation requires NSD3, revealing unexpected complexity in NSD3- dependent neural crest gene regulation. In addition, by temporally limiting expression of a dominant negative to migratory stages, we identify a novel, direct requirement for NSD3- related methyltransferase activity in neural crest migration. These results identify NSD3 as the first protein methyltransferase essential for neural crest gene expression during specification and show that NSD3-related methyltransferase activity independently regulates migration.
AB - Neural crest precursors express genes that cause them to become migratory, multipotent cells, distinguishing them from adjacent stationary neural progenitors in the neurepithelium. Histone methylation spatiotemporally regulates neural crest gene expression; however, the protein methyltransferases active in neural crest precursors are unknown. Moreover, the regulation of methylation during the dynamic process of neural crest migration is unclear. Here we show that the lysine methyltransferase NSD3 is abundantly and specifically expressed in premigratory and migratory neural crest cells. NSD3 expression commences before up-regulation of neural crest genes, and NSD3 is necessary for expression of the neural plate border gene Msx1, as well as the key neural crest transcription factors Sox10, Snail2, Sox9, and FoxD3, but not gene expression generally. Nevertheless, only Sox10 his tone H3 lysine 36 dimethylation requires NSD3, revealing unexpected complexity in NSD3- dependent neural crest gene regulation. In addition, by temporally limiting expression of a dominant negative to migratory stages, we identify a novel, direct requirement for NSD3- related methyltransferase activity in neural crest migration. These results identify NSD3 as the first protein methyltransferase essential for neural crest gene expression during specification and show that NSD3-related methyltransferase activity independently regulates migration.
UR - http://www.scopus.com/inward/record.url?scp=84919494924&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84919494924&partnerID=8YFLogxK
U2 - 10.1091/mbc.E13-12-0744
DO - 10.1091/mbc.E13-12-0744
M3 - Article
C2 - 25318671
AN - SCOPUS:84919494924
SN - 1059-1524
VL - 25
SP - 4174
EP - 4186
JO - Molecular biology of the cell
JF - Molecular biology of the cell
IS - 25
ER -