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The Jumonji Domain-Containing Histone Demethylase Homolog 1D/lysine Demethylase 7A (JHDM1D/KDM7A) Is an Epigenetic Activator of RHOJ Transcription in Breast Cancer Cells.

ABSTRACT: The small GTPase RHOJ is a key regulator of breast cancer metastasis by promoting cell migration and invasion. The prometastatic stimulus TGF-β activates RHOJ transcription via megakaryocytic leukemia 1 (MKL1). The underlying epigenetic mechanism is not clear. Here, we report that MKL1 deficiency led to disrupted assembly of the RNA polymerase II preinitiation complex on the RHOJ promoter in breast cancer cells. This could be partially explained by histone H3K9/H3K27 methylation status. Further analysis confirmed that the H3K9/H3K27 dual demethylase JHDM1D/KDM7A was essential for TGF-β-induced RHOJ transcription in breast cancer cells. MKL1 interacted with and recruited KDM7A to the RHOJ promoter to cooperatively activate RHOJ transcription. KDM7A knockdown attenuated migration and invasion of breast cancer cells in vitro and mitigated the growth and metastasis of breast cancer cells in nude mice. KDM7A expression level, either singularly or in combination with that of RHOJ, could be used to predict prognosis in breast cancer patients. Of interest, KDM7A appeared to be a direct transcriptional target of TGF-β signaling. A SMAD2/SMAD4 complex bound to the KDM7A promoter and mediated TGF-β-induced KDM7A transcription. In conclusion, our data unveil a novel epigenetic mechanism whereby TGF-β regulates the transcription of the prometastatic small GTPase RHOJ. Screening for small-molecule inhibitors of KDM7A may yield effective therapeutic solutions to treat malignant breast cancers.

SUBMITTER: Zhang Z

PROVIDER: S-EPMC8262595 | biostudies-literature |

REPOSITORIES: biostudies-literature

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The Lysine Demethylase KDM7A Regulates Immediate Early Genes in Neurons.

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Project description: Not available

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The histone lysine demethylase <i>KDM7A</i> is required for normal development and first cell lineage specification in porcine embryos.

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The lysine demethylase KDM7A regulates immediate early genes in neurons [CUT&Tag]

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2023-08-21 | GSE236352 | GEO

Jumonji C domain-containing protein 12 is a Histone H3 Lysine 27 Demethylase

Project description:This SuperSeries is composed of the following subset Series: GSE25444: Differential gene expression in ref6-1 GSE25446: Genome-wide comparison of H3K27me3 difference between ref6-1 and wild type Col Refer to individual Series

2011-05-24 | E-GEOD-25447 | biostudies-arrayexpress

Jumonji C domain-containing protein 12 is a Histone H3 Lysine 27 Demethylase

Project description:This SuperSeries is composed of the SubSeries listed below.

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Histone Lysine Demethylase Inhibitors.

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