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Transcriptional and post-transcriptional control of adipocyte differentiation by Jumonji domain-containing protein 6.

ABSTRACT: Jumonji domain-containing protein 6 (JMJD6) is a nuclear protein involved in histone modification, transcription and RNA processing. Although JMJD6 is crucial for tissue development, the link between its molecular functions and its roles in any given differentiation process is unknown. We report that JMJD6 is required for adipogenic gene expression and differentiation in a manner independent of Jumonji C domain catalytic activity. JMJD6 knockdown led to a reduction of C/EBP? and C/EBP? protein expression without affecting mRNA levels in the early phase of differentiation. However, ectopic expression of C/EBP? and C/EBP? did not rescue differentiation. Further analysis demonstrated that JMJD6 was associated with the Ppar?2 and Cebp? loci and putative enhancers. JMJD6 was previously found associated with bromodomain and extra-terminal domain (BET) proteins, which can be targeted by the bromodomain inhibitor JQ1. JQ1 treatment prevented chromatin binding of JMJD6, Ppar?2 and Cebp? expression, and adipogenic differentiation, yet had no effect on C/EBP? and C/EBP? expression or chromatin binding. These results indicate dual roles for JMJD6 in promoting adipogenic gene expression program by post-transcriptional regulation of C/EBP? and C/EBP? and direct transcriptional activation of Ppar?2 and Cebp? during adipocyte differentiation.

SUBMITTER: Hu YJ

PROVIDER: S-EPMC4652747 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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Transcriptional and post-transcriptional control of adipocyte differentiation by Jumonji domain-containing protein 6.

Hu Yu-Jie YJ Belaghzal Houda H Hsiao Wen-Yu WY Qi Jun J Bradner James E JE Guertin David A DA Sif Saïd S Imbalzano Anthony N AN

Nucleic acids research 20150627 16

Jumonji domain-containing protein 6 (JMJD6) is a nuclear protein involved in histone modification, transcription and RNA processing. Although JMJD6 is crucial for tissue development, the link between its molecular functions and its roles in any given differentiation process is unknown. We report that JMJD6 is required for adipogenic gene expression and differentiation in a manner independent of Jumonji C domain catalytic activity. JMJD6 knockdown led to a reduction of C/EBPβ and C/EBPδ protein e ...[more]

PMID: 26117538

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Project description:BackgroundHistone demethylase RIOX2 was cloned as a c-Myc downstream gene involved in cell proliferation and has been implicated as an oncogenic factor in multiple tumor types. Its expression profiles and correlation with disease progression in prostate cancers are unknown.MethodsTranscriptomic profiles of Jumanji domain-containing protein genes were assessed using multiple public expression datasets generated from RNA-seq and cDNA microarray assays. RIOX2 protein expression was assessed using an immunohistochemistry approach on a tissue section array from benign and malignant prostate tissues. Gene expression profiles were analyzed using the bioinformatics software R package. Western blot assay examined androgen stimulation on RIOX2 protein expression in LNCaP cells.ResultsAmong 35 Jumanji domain-containing protein genes, 12 genes were significantly upregulated in prostate cancers compared to benign compartments. COX regression analysis identified that the ribosomal oxygenase 2 (RIOX2) gene was the only one significantly associated with disease-specific survival outcomes in prostate cancer patients. RIOX2 upregulation was confirmed at the protein levels using immunohistochemical assays on prostate cancer tissue sections. Meanwhile, RIOX2 upregulation was associated with clinicopathological features, including late-stage diseases, adverse Gleason scores, TP53 gene mutation, and disease-free status. In castration-resistant prostate cancers (CRPC), RIOX2 expression was positively correlated with AR signaling index but negatively correlated with the neuroendocrinal progression index. However, androgen treatment had no significant stimulatory effect on RIOX2 expression, indicating a parallel but not a causative effect of androgen signaling on RIOX2 gene expression. Further analysis discovered that RIOX2 expression was tightly correlated with its promoter hypomethylation and MYC gene expression, consistent with the notion that RIOX2 was a c-Myc target gene.ConclusionThe Jumanji domain-containing protein RIOX2 was significantly overexpressed in prostate cancer, possibly due to c-Myc upregulation. RIOX2 upregulation was identified as an independent prognostic factor for disease-specific survival.

Dataset Information

Transcriptional and post-transcriptional control of adipocyte differentiation by Jumonji domain-containing protein 6.

Publications

Transcriptional and post-transcriptional control of adipocyte differentiation by Jumonji domain-containing protein 6.

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