Abstract
JMJD3 H3K27me3 demethylase plays an important role in the transcriptional response to different signaling pathways; however, the mechanism by which it facilitates transcription has been unclear. Here we show that JMJD3 regulates transcription of transforming growth factor β (TGFβ)-responsive genes by promoting RNA polymerase II (RNAPII) progression along the gene bodies. Using chromatin immunoprecipitation followed by sequencing experiments, we show that, upon TGFβ treatment, JMJD3 and elongating RNAPII colocalize extensively along the intragenic regions of TGFβ target genes. According to these data, genome-wide analysis shows that JMJD3-dependent TGFβ target genes are enriched in H3K27me3 before TGFβ signaling pathway activation. Further molecular analyses demonstrate that JMJD3 demethylates H3K27me3 along the gene bodies, paving the way for the RNAPII progression. Overall these findings uncover the mechanism by which JMJD3 facilitates transcriptional activation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Basic Helix-Loop-Helix Transcription Factors / genetics
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Basic Helix-Loop-Helix Transcription Factors / metabolism
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Chromatin Immunoprecipitation
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Cyclin-Dependent Kinase 9 / metabolism
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Genome
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HEK293 Cells
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Histones / metabolism*
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Humans
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Jumonji Domain-Containing Histone Demethylases / physiology*
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Methylation
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Mice
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism
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Neural Stem Cells
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Phosphorylation
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Promoter Regions, Genetic
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Protein Binding
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Protein Processing, Post-Translational*
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RNA Polymerase II / metabolism*
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Sequence Analysis, DNA
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Smad3 Protein / metabolism
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Transcription Initiation Site
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Transcription, Genetic*
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Transforming Growth Factor beta / physiology
Substances
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Basic Helix-Loop-Helix Transcription Factors
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Histones
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Nerve Tissue Proteins
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Neurog2 protein, mouse
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Smad3 Protein
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Smad3 protein, mouse
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Transforming Growth Factor beta
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Jumonji Domain-Containing Histone Demethylases
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Kdm6b protein, mouse
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Cdk9 protein, mouse
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Cyclin-Dependent Kinase 9
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RNA Polymerase II