Transcriptomics,Genomics

Dataset Information

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A chromatin-modifying function of JNK during stem cell differentiation


ABSTRACT: Signaling mediates cellular responses to extracellular stimuli. The c-Jun NH2-terminal kinase (JNK) pathway exemplifies one sub-group of Mitogen-activated protein (MAP) kinases, which besides established functions in stress response, also contributes to developmental processes by an unknown mechanism 1-4. Here we show by genome-wide location analysis that JNK binds directly to a large set of active promoters during differentiation of stem cells to neurons. Bound promoters are not enriched for the canonical AP?1 target sites yet for binding motifs for the transcription factor NF?Y. NF-Y indeed occupies these predicted sites genome-wide in vivo and overexpression of a dominant-negative form of NF?YA reduces JNK presence on chromatin. Histone H3 is a substrate for JNK kinase activity in vitro and JNK bound promoters are preferentially enriched for Histone H3 phosphorylated at Serine 10. Inhibition of JNK signaling in postmitotic neurons reduces this chromatin phosphorylation as well as expression of target genes. Together this establishes MAP kinase binding and function on chromatin at a novel class of target genes during stem cell differentiation. Our Dataset comprises 5 ChIP-seq samples using chromatin from ES, NP and TN cells which was immunoprecipitated, using antibodies against H3K27me3, H3K4me2, RNA Pol II, JNK1/3 and NF-YA. From the same cells we generated biological replicates of RNA-seq data.

ORGANISM(S): Mus musculus  

SUBMITTER: Christiane Wirbelauer   Michael B Stadler  Dirk Schuebeler  Renato Paro  Vijay Tiwari  Dirk Schübeler  Christian Beisel 

PROVIDER: E-GEOD-25532 | ArrayExpress | 2011-12-18

SECONDARY ACCESSION(S): SRP004709GSE25532SRP004710PRJNA142433

REPOSITORIES: GEO, ArrayExpress, ENA

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Publications

Target genes of Topoisomerase IIβ regulate neuronal survival and are defined by their chromatin state.

Tiwari Vijay K VK   Burger Lukas L   Nikoletopoulou Vassiliki V   Deogracias Ruben R   Thakurela Sudhir S   Wirbelauer Christiane C   Kaut Johannes J   Terranova Remi R   Hoerner Leslie L   Mielke Christian C   Boege Fritz F   Murr Rabih R   Peters Antoine H F M AH   Barde Yves-Alain YA   Schübeler Dirk D  

Proceedings of the National Academy of Sciences of the United States of America 20120402 16


Topoisomerases are essential for DNA replication in dividing cells, but their genomic targets and function in postmitotic cells remain poorly understood. Here we show that a switch in the expression from Topoisomerases IIα (Top2α) to IIβ (Top2β) occurs during neuronal differentiation in vitro and in vivo. Genome-scale location analysis in stem cell-derived postmitotic neurons reveals Top2β binding to chromosomal sites that are methylated at lysine 4 of histone H3, a feature of regulatory regions  ...[more]

Publication: 1/2

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