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Title:
A chromatin-modifying function of JNK during stem cell differentiation | Nature Genetics
Description:
Dirk Schübeler, Michael Stadler and colleagues show that the c-Jun NH2-terminal kinase (JNK) binds directly to active promoters during the differentiation of stem cells to neurons and targets histone H3 serine 10 for phosphorylation. Signaling mediates cellular responses to extracellular stimuli. The c-Jun NH2-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 mechanism1,2,3,4. 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.
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Topics {✒️}
nature portfolio permissions reprints privacy policy open access database nf-κb–dependent gene expression open software development c-jun nh2-terminal kinase author information authors c-jun n-terminal kinases advertising cytokine-induced gene expression european research council social media novartis research foundation jun n-terminal kinase dominant-negative nf-ya reduces nature 461 nature 438 nature 423 nature tools lineage-specific polycomb targets italy biomedical research mitogen-activated protein kinases stress-activated kinase 1/2 msk-dependent h3k27me3s28 phosphorylation cell type-dependent control transcription factor-binding profiles map kinase–mediated phosphorylation research springerlink instant access myc-dependent transcriptional activation genome-wide location analysis mitogen-activated protein permissions hp1-chromatin binding p38 mapk pathways annexin a1 expression stem cell differentiation quantitative genomics facility friedrich miescher institute iκb kinase-α drosophila thorax development early embryonic neurogenesis privacy scaffold protein revealed dominant-negative analogs transcription factor nf short dna sequences
Questions {❓}
- AP-1—the Jun proteins: oncogenes or tumor suppressors in disguise?
- Histone H3 phosphorylation: universal code or lineage specific dialects?
- Phosphorylation of serine 10 in histone H3, what for?
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headline:A chromatin-modifying function of JNK during stem cell differentiation
description:Dirk Schübeler, Michael Stadler and colleagues show that the c-Jun NH2-terminal kinase (JNK) binds directly to active promoters during the differentiation of stem cells to neurons and targets histone H3 serine 10 for phosphorylation. Signaling mediates cellular responses to extracellular stimuli. The c-Jun NH2-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 mechanism1,2,3,4. 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.
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