title: A chromatin-modifying function of JNK during stem cell differentiation.
abstract: Signaling mediates cellular responses to extracellular stimuli. The c-Jun NH(2)-terminal kinase (JNK) pathway exemplifies one subgroup of the mitogen-activated protein (MAP) kinases, which, besides having established functions in stress response, also contribute to development by an unknown mechanism. We show by genome-wide location analysis that JNK binds to a large set of active promoters during the differentiation of stem cells into neurons. JNK-bound promoters are enriched with binding motifs for the transcription factor NF-Y but not for AP-1. NF-Y occupies these predicted sites, and overexpression of dominant-negative NF-YA reduces the JNK presence on chromatin. We find that histone H3 Ser10 (H3S10) is a substrate for JNK, and JNK-bound promoters are enriched for H3S10 phosphorylation. Inhibition of JNK signaling in post-mitotic neurons reduces phosphorylation at H3S10 and the expression of target genes. These results establish MAP kinase binding and function on chromatin at a novel class of target genes during stem cell differentiation.
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
authors.forename: Vijay K
authors.initials: VK
authors.lastname: Tiwari
authors.forename: Michael B
authors.initials: MB
authors.lastname: Stadler
authors.forename: Christiane
authors.initials: C
authors.lastname: Wirbelauer
authors.forename: Renato
authors.initials: R
authors.lastname: Paro
authors.forename: Dirk
authors.initials: D
authors.lastname: Schübeler
authors.forename: Christian
authors.initials: C
authors.lastname: Beisel
mesh_terms: D000818:Animals; D023081:CCAAT-Binding Factor / Q000378:metabolism; D002454:Cell Differentiation; D002843:Chromatin / Q000378:metabolism*; D053595:Embryonic Stem Cells; D005786:Gene Expression Regulation; D048670:MAP Kinase Kinase 4 / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000235:genetics; D051379:Mice; D058953:Neural Stem Cells; D009474:Neurons / Q000502:physiology; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D013234:Stem Cells; D015854:Up-Regulation
chemical_list: D023081:CCAAT-Binding Factor; D002843:Chromatin; C402244:nuclear factor Y; D048670:MAP Kinase Kinase 4