Genome-wide analysis reveals that Smad3 and JMJD3 HDM co-activate the neural developmental program.
Neural development requires crosstalk between signaling pathways and chromatin. In this study, we demonstrate that neurogenesis is promoted by an interplay between the TGFβ pathway and the H3K27me3 histone demethylase (HDM) JMJD3. Genome-wide analysis showed that JMJD3 is targeted to gene promoters by Smad3 in neural stem cells (NSCs) and is essential to activate TGFβ-responsive genes. In vivo experiments in chick spinal cord revealed that the generation of neurons promoted by Smad3 is dependent on JMJD3 HDM activity. Overall, these findings indicate that JMJD3 function is required for the TGFβ developmental program to proceed.
Department of Molecular Genomics, Instituto de Biología Molecular de Barcelona, Consejo Superior de Investigaciones Científicas, Barcelona, Spain.
Conchi
C
Estarás
Naiara
N
Akizu
Alejandra
A
García
Sergi
S
Beltrán
Xavier
X
de la Cruz
Marian A
MA
Martínez-Balbás
D000818:Animals; D002642:Chick Embryo; D015509:Developmental Biology / Q000379:methods*; D005786:Gene Expression Regulation; D055106:Genome-Wide Association Study; D049452:Green Fluorescent Proteins / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D009474:Neurons / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D010766:Phosphorylation; D051900:Smad3 Protein / Q000378:metabolism*; D013116:Spinal Cord / Q000196:embryology; D016212:Transforming Growth Factor beta / Q000378:metabolism
C497790:SMAD3 protein, human; D051900:Smad3 Protein; C497791:Smad3 protein, mouse; D016212:Transforming Growth Factor beta; D049452:Green Fluorescent Proteins; D056484:Jumonji Domain-Containing Histone Demethylases; C524220:KDM6B protein, human; C523761:Kdm6b protein, mouse