Jmjd3 and UTX Play a Demethylase-Independent Role in Chromatin Remodeling to Regulate T-Box Family Member-Dependent Gene Expression

Miller, Sara A.; Mohn, Sarah E.; Weinmann, Amy S.

doi:10.1016/j.molcel.2010.10.028

Cited by 295 publications

(303 citation statements)

References 41 publications

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“…A demethylase-independent role of JMJD3 has been described in differentiated cells (T-helper 1 cells) in which the epigenetic profile is already established and fulfills another role. Specifically, JMJD3 mediates a functional interaction between T-bet, a T-box transcription factor, and a Brg1-containing switch/sucrose nonfermentable (SWI/SNF) remodeling complex (50). We have confirmed that JMJD3 acts during the active demethylation process of early embryo development, but we are not able to rule out the possibility that JMJD3 also enacts demethylase-independent consequences during embryo development.…”

Section: Discussionmentioning

confidence: 70%

Jumonji domain-containing protein 3 regulates histone 3 lysine 27 methylation during bovine preimplantation development

Cánovas

Cibelli

Ross

2012

Proc. Natl. Acad. Sci. U.S.A.

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Understanding the mechanisms of epigenetic remodeling that follow fertilization is a fundamental step toward understanding the bases of early embryonic development and pluripotency. Extensive and dynamic chromatin remodeling is observed after fertilization, including DNA methylation and histone modifications. These changes underlie the transition from gametic to embryonic chromatin and are thought to facilitate embryonic genome activation. In particular, trimethylation of histone 3 lysine 27 (H3K27me3) is associated with gene-specific transcription repression. Global levels of this epigenetic mark are high in oocyte chromatin and decrease to minimal levels at the time of embryonic genome activation. We provide evidence that the decrease in H3K27me3 observed during early development is cell-cycle independent, suggesting an active mechanism for removal of this epigenetic mark. Among H3K27me3-specific demethylases, Jumonji domain-containing protein 3 (JMJD3), but not ubiquitously transcribed tetratricopeptide repeat X (UTX), present high transcript levels in oocytes. Soon after fertilization JMJD3 protein levels increase, concurrent with a decrease in mRNA levels. This pattern of expression suggests maternal inheritance of JMJD3. Knockdown of JMJD3 by siRNA injection in parthenogenetically activated metaphase II oocytes resulted in inhibition of the H3K27me3 decrease normally observed in preimplantation embryos. Moreover, knockdown of JMJD3 in oocytes reduced the rate of blastocyst development. Overall, these results indicate that JMJD3 is involved in active demethylation of H3K27me3 during early embryo development and that this mark plays an important role during the progression of embryos to blastocysts.G amete nuclei undergo extensive chromatin remodeling soon after fertilization, including alterations to DNA methylation levels and posttranslational histone tail modification. These changes are known to influence chromatin structure and transcriptional readout (1) and also to promote embryonic genome activation (EGA) (2), which occurs in humans and cows after three to four cell divisions (3-5). Because the first few cell divisions occur without embryonic gene transcription, maternally inherited mRNA and proteins present in the oocyte are likely responsible for inducing these epigenetic changes (6).Histone lysine methylation is involved in transcriptional repression and/or activation and plays a key role during lineage specification and cell differentiation (7). Di-and trimethylation of histone 3 lysine 27 (H3K27) are catalyzed by the polycomb repressive complex 2 (PRC2), which has three essential components: enhancer of zeste homolog 2 (EZH2), embryonic ectoderm development (EED), and suppressor of zeste 12 (SUZ12) (8-10). These epigenetic marks are specifically associated with gene repression (11) and are typical of many key developmental genes in embryonic stem cells, stem cell maintenance (12-14), and regulation of pluripotency (15). In mouse embryos, asymmetric distribution of trimethylated H3K27 (H3K27me3) i...

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Section: Discussionmentioning

confidence: 70%

Jumonji domain-containing protein 3 regulates histone 3 lysine 27 methylation during bovine preimplantation development

Cánovas

Cibelli

Ross

2012

Proc. Natl. Acad. Sci. U.S.A.

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“…This result is consistent with the recent finding that Jmjd3 functions in control- [19] . Jmjd3 also has demethylase-independent functions: Miller et al [35] reported that Jmjd3 mediates a functional interaction between the lineage-defining T-box transcription factor family member and its target genes. T-box transcription factor family members, such as Brachyury and Tbx5, are critical regulators of cardiac differentiation [36] .…”

Section: Discussionmentioning

confidence: 99%

Expression profiles of histone lysine demethylases during cardiomyocyte differentiation of mouse embryonic stem cells

et al. 2014

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Aim: Histone lysine demethylases (KDMs) control the lineage commitments of stem cells. However, the KDMs involved in the determination of the cardiomyogenic lineage are not fully defined. The aim of this study was to investigate the expression profiles of KDMs during the cardiac differentiation of mouse embryonic stem cells (mESCs). Methods: An in vitro cardiac differentiation system of mESCs with Brachyury (a mesodermal specific marker) and Flk-1 + /Cxcr4 + (dual cell surface biomarkers) selection was used. The expression profiles of KDMs during differentiation were analyzed using Q-PCR. To understand the contributions of KDMs to cardiomyogenesis, the mESCs on differentiation d 3.5 were sorted by FACS into Brachyury + cells and Brachyury -cells, and mESCs on d 5.5 were sorted into Flk-1 + /Cxcr4 + and Flk-1 -/Cxcr4 -cells. Results: mESCs were differentiated into spontaneously beating cardiomyocytes that were visible in embryoid bodies (EBs) on d 7. On d 12-14, all EBs developed spontaneously beating cardiomyocytes. Among the 16 KDMs examined, the expression levels of Phf8, Jarid1a, Jhdm1d, Utx, and Jmjd3 were increased by nearly 2-6-fold on d 14 compared with those on d 0. Brachyury + cells showed higher expression levels of Jmjd3, Jmjd2a and Jhdm1d than Brachyury -cells. A higher level of Jmjd3 was detected in Flk-1 + /Cxcr4 + cells, whereas the level of Jmjd2c was lower in both Brachyury + cells and Flk-1 + /Cxcr4 + cells. Conclusion: KDMs may play important roles during cardiomyogenesis of mESCs. Our results provide a clue for further exploring the roles of KDMs in the cardiac lineage commitment of mESCs and the potential interference of cardiomyogenesis.

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“…PRC1, in turn, can ubiquitinate lysine 119 of histone H2A, leading to a closing of the chromatin structure [46,189]. Similarly, KDM3A and KDM6 demethylases play a role in chromatin remodeling by linking transcription factors with the SWI/SNF chromatin remodeling complex [190,191]. Since these proteins regulate the chromatin compaction associated with genes involved in carcinogenesis and cell proliferation, mutation or depletion of histone demethylases could interfere with these biological processes.…”

Section: Beyond the Histone Demethylase Functionmentioning

confidence: 99%

Lysine-Specific Histone Demethylases Contribute to Cellular Differentiation and Carcinogenesis

Verde

Querol-Paños²,

Cebrià-Costa³

et al. 2017

Epigenomes

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Histone modifications regulate chromatin structure, gene transcription, and other nuclear processes. Among the histone modifications, methylation has been considered to be a stable, irreversible process due to the slow turnover of methyl groups in chromatin. However, the discovery of three different classes of lysine-specific demethylases-KDM1, Jumonji domain-containing demethylases, and lysyl oxidase-like 2 protein-has drastically changed this view, suggesting a role for dynamic histone methylation in different biological process. In this review, we describe the different mechanisms that these enzymes use to remove lysine histone methylation and discuss their role during physiological (cell differentiation) and pathological (carcinogenesis) processes.

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Jmjd3 and UTX Play a Demethylase-Independent Role in Chromatin Remodeling to Regulate T-Box Family Member-Dependent Gene Expression

Cited by 295 publications

References 41 publications

Jumonji domain-containing protein 3 regulates histone 3 lysine 27 methylation during bovine preimplantation development

Jumonji domain-containing protein 3 regulates histone 3 lysine 27 methylation during bovine preimplantation development

Expression profiles of histone lysine demethylases during cardiomyocyte differentiation of mouse embryonic stem cells

Lysine-Specific Histone Demethylases Contribute to Cellular Differentiation and Carcinogenesis

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