Histone demethylase JARID1B/KDM5B is a corepressor of TIEG1/KLF10

Kim, Joanna J.; Shin, Sook; Subramaniam, Malayannan; Bruinsma, Elizabeth S.; Kim, Tae‐Dong; Hawse, John R.; Spelsberg, Thomas C.; Janknecht, Ralf

doi:10.1016/j.bbrc.2010.09.068

Cited by 50 publications

(49 citation statements)

References 38 publications

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“…It is, however, unclear how chromatin-modifying enzymes are recruited to a specific site. DNA binding of JARID1B depends on the ARID site, 28,29 whereas the demethylase activity is located in the JmjC-domain, a structure similar to the hypoxia-inducible factor hydroxylation prolyl hydroxylases. 30 In fact, demethylation by JARID1B is a 2-step mechanism: the nitrogen is first hydroxylated and subsequently, the methyl group cleaved of.…”

Section: Discussionmentioning

confidence: 99%

Epigenetic Regulation of Angiogenesis by JARID1B-Induced Repression of HOXA5

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Hitzel

et al. 2015

ATVB

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Objective-Altering endothelial biology through epigenetic modifiers is an attractive novel concept, which is, however, just in its beginnings. We therefore set out to identify chromatin modifiers important for endothelial gene expression and contributing to angiogenesis. Approach and Results-To identify chromatin modifying enzymes in endothelial cells, histone demethylases were screened by microarray and polymerase chain reaction. The histone 3 lysine 4 demethylase JARID1B was identified as a highly expressed enzyme at the mRNA and protein levels. Knockdown of JARID1B by shRNA in human umbilical vein endothelial cells attenuated cell migration, angiogenic sprouting, and tube formation. Similarly, pharmacological inhibition and overexpression of a catalytic inactive JARID1B mutant reduced the angiogenic capacity of human umbilical vein endothelial cells. To identify the in vivo relevance of JARID1B in the vascular system, Jarid1b knockout mice were studied. As global knockout results in increased mortality and developmental defects, tamoxifen-inducible and endothelial-specific knockout mice were generated. Acute knockout of Jarid1b attenuated retinal angiogenesis and endothelial sprout outgrowth from aortic segments. To identify the underlying mechanism, a microarray experiment was performed, which led to the identification of the antiangiogenic transcription factor HOXA5 to be suppressed by JARID1B. Importantly, downregulation or inhibition of JARID1B, but not of JARID1A and JARID1C, induced HOXA5 expression in human umbilical vein endothelial cells. Consistently, chromatin immunoprecipitation revealed that JARID1B occupies and reduces the histone 3 lysine 4 methylation levels at the HOXA5 promoter, demonstrating a direct function of JARID1B in endothelial HOXA5 gene regulation. Conclusions-JARID1B, by suppressing HOXA5, maintains the endothelial angiogenic capacity in a demethylasedependent manner.

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Section: Discussionmentioning

confidence: 99%

Epigenetic Regulation of Angiogenesis by JARID1B-Induced Repression of HOXA5

Fork

Hitzel

et al. 2015

ATVB

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“…After additional 48 hr, infected cells were selected with 2 μg/ml of puromycin for 7 days and pooled for analysis [15]. Flag-JARID1B mutants were generated from pEV-Flag-JARID1B [53] using QuikChange II XL Site-Directed Mutagenesis Kit (Agilent Technologies, CA) according to manufacturer's instruction. The nucleotides sequences of various primers for SKP2 shRNA, and JARID1B mutants are shown in Supplementary Table S1.…”

Section: Methodsmentioning

confidence: 99%

“…Briefly, HEK293T cells were transfected with Flag tagged JARID1B [53] or JARID1B mutants, HA tagged Ubiquitin WT or Ubiquitin mutants (K48-only and K63-only) [55], Myc tagged TRAF6 [56], along with or without Myc tagged SKP2 plasmids as indicated for 24 hr, then treated with 10 μM of MG132 for additional 6 hr. Cells were lysed in 100 μl of SDS lysis buffer containing 50 mM Tris-HCl pH 7.5, 150 mM NaCl and 1% SDS, and boiled for 10 min at 95°C.…”

Section: Methodsmentioning

confidence: 99%

SKP2 inactivation suppresses prostate tumorigenesis by mediating JARID1B ubiquitination

Liu

et al. 2014

Oncotarget

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Aberrant elevation of JARID1B and histone H3 lysine 4 trimethylation (H3K4me3) is frequently observed in many diseases including prostate cancer (PCa), yet the mechanisms on the regulation of JARID1B and H3K4me3 through epigenetic alterations still remain poorly understood. Here we report that Skp2 modulates JARID1B and H3K4me3 levels in vitro in cultured cells and in vivo in mouse models. We demonstrated that Skp2 inactivation decreased H3K4me3 levels, along with a reduction of cell growth, cell migration and malignant transformation of Pten/Trp53 double null MEFs, and further restrained prostate tumorigenesis of Pten/Trp53 mutant mice. Mechanistically, Skp2 decreased the K63-linked ubiquitination of JARID1B by E3 ubiquitin ligase TRAF6, thus decreasing JARID1B demethylase activity and in turn increasing H3K4me3. In agreement, Skp2 deficiency resulted in an increase of JARID1B ubiquitination and in turn a reduction of H3K4me3, and induced senescence through JARID1B accumulation in nucleoli of PCa cells and prostate tumors of mice. Furthermore, we showed that the elevations of Skp2 and H3K4me3 contributed to castration-resistant prostate cancer (CRPC) in mice, and were positively correlated in human PCa specimens. Taken together, our findings reveal a novel network of SKP2- JARID1B, and targeting SKP2 and JARID1B may be a potential strategy for PCa control.

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“…61 Both plasmids were kindly provided by Ralf Janknecht (University of Oklahoma Health Sciences Center). FLAG-KDM5D was expressed from the vector pFLAG-CMV2JARID1D 62 and was kindly obtained from Ramin Shiekhattar (The Wistar Institute).…”

Section: Methodsmentioning

confidence: 99%