Histone Demethylase Jumonji AT-rich Interactive Domain 1B (JARID1B) Controls Mammary Gland Development by Regulating Key Developmental and Lineage Specification Genes

Zou, Mike R.; Cao, Jian; Liu, Zongzhi; Huh, Sung Jin; Polyák, Kornélia; Yan, Qin

doi:10.1074/jbc.m114.570853

Cited by 51 publications

(56 citation statements)

References 50 publications

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“…Of these enzymes, KDM5A, KDM5B and KDM5C have been shown to interact with the HDACcontaining complexes, such as NCoR and Sin3 complexes, and are involved in a variety of biological processes including cell differentiation, development, senescence, signal transduction, and metabolic processes (Tan et al, 2003;Barrett et al, 2007;Hayakawa et al, 2007;Klose et al, 2007;Tahiliani et al, 2007;van Oevelen et al, 2008;Hayakawa & Nakayama, 2010;Liefke et al, 2010;Huang et al, 2011;Zou et al, 2014). In addition, KDM5D, a homolog of mouse SMCY, was first isolated in the short arm of Y chromosome (Agulnik et al, 1994;Kent-First et al, 1996).…”

Section: Kdm5 Subfamilymentioning

confidence: 98%

Epigenetic targets and drug discovery Part 2: Histone demethylation and DNA methylation

Liu

Lau

et al. 2015

Pharmacology & Therapeutics

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Section: Kdm5 Subfamilymentioning

confidence: 98%

Epigenetic targets and drug discovery Part 2: Histone demethylation and DNA methylation

Liu

Lau

et al. 2015

Pharmacology & Therapeutics

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“…JARID1 proteins are also implicated in later development and adult tissue homeostasis, including myogenic differentiation of embryonic fibroblasts [111]. A role for JARID1B in postnatal mammary gland development was observed in a viable strain of JARID1B knockout mice [33] and mice where only JARID1B’s ARID domain was deleted [106]. The latter mice display a phenotype where mammary growth was delayed at puberty and early pregnancy.…”

Section: Overview Of Jarid1 Family Functionmentioning

confidence: 99%

“…For instance, JARID1B deficiency in pubescent mice impaired expression of multiple regulators of mammary morphogenesis including FOXA1. Here JARID1B was required to recruit GATA3 to the FOXA1 promoter in order to activate transcription, although the demethylase dependence of this effect is unclear [33]. JARID1 demethylases may also stabilize active transcription by mediating cyclic turnover of H3K4me3 levels.…”

Section: Jarid1-mediated Transcriptional Regulationmentioning

confidence: 99%

JARID1 Histone Demethylases: Emerging Targets in Cancer

et al. 2017

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JARID1 proteins are histone demethylases that both regulate normal cell fates during development and contribute to the epigenetic plasticity that underlies malignant transformation. This H3K4 demethylase family participates in multiple repressive transcriptional complexes at promoters and has broader regulatory effects on chromatin that remain ill-defined. There is growing understanding of the oncogenic and tumor suppressive functions of JARID1 proteins, which are contingent on cell context and the protein isoform. Their contributions to stem cell-like de-differentiation, tumor aggressiveness, and therapy resistance in cancer have sustained interest in the development of JARID1 inhibitors. Here we review the diverse and context-specific functions of the JARID1 proteins that may impact the utilization of emerging targeted inhibitors of this histone demethylase family in cancer therapy.

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“…5,8,11,12,16,17 Therefore, genetic deletion of JARID1B impairs mouse and porcine embryonic development. [18][19][20][21] Considering its effect on gene regulation, we hypothesized that JARID1B affects the expression of endothelial genes and examined the consequences on angiogenesis in human umbilical vein ECs (HUVECs), tamoxifen-inducible conditional, and in the endothelial-specific Jarid1b knockout mouse.…”

mentioning

confidence: 99%

Epigenetic Regulation of Angiogenesis by JARID1B-Induced Repression of HOXA5

Fork

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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Histone Demethylase Jumonji AT-rich Interactive Domain 1B (JARID1B) Controls Mammary Gland Development by Regulating Key Developmental and Lineage Specification Genes

Cited by 51 publications

References 50 publications

Epigenetic targets and drug discovery Part 2: Histone demethylation and DNA methylation

Epigenetic targets and drug discovery Part 2: Histone demethylation and DNA methylation

JARID1 Histone Demethylases: Emerging Targets in Cancer

Epigenetic Regulation of Angiogenesis by JARID1B-Induced Repression of HOXA5

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