RNA polymerase II progression through H3K27me3-enriched gene bodies requires JMJD3 histone demethylase

Estarás, Conchi; Fueyo, Raquel; Akizu, Naiara; Beltrán, Sergi; Martínez‐Balbás, Marian A.

doi:10.1091/mbc.e12-07-0561

Cited by 49 publications

(54 citation statements)

References 44 publications

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“…Previous results also suggested that KDM6B activates gene transcription by promoting transcriptional elongation, which is associated with RNA polymerase II and related elongation factors [25,26]. These results indicated that up-regulation of KDM6B should be essential for gene expression of specific hypoxia response gene under hypoxia.…”

Section: Discussionmentioning

confidence: 68%

Regulation of histone demethylase KDM6B by hypoxia-inducible factor-2α

Guo¹,

Tian²,

Wang³

et al. 2015

ABBS

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Lysine (K)-specific demethylase 6B (KDM6B) is a histone H3K27 demethylase, which specifically catalyzes the demethylation of H3 lysine-27 tri/dimethylation (H3K27me3/2). KDM6B can activate gene transcription by promoting transcriptional elongation which is associated with RNA polymerase II and related elongation factors. So KDM6B is important for the regulation of gene expression. Previous studies have indicated that several histone demethylases such as KDM3A, KDM4B, and KDM4C are regulated by hypoxia-inducible factor (HIF). But, the effect of hypoxia on KDM6B is not fully understood. In this study, we found that the expression levels of KDM6B mRNA and protein are modestly up-regulated under hypoxia (1% O 2 ) or mimic hypoxia (desferrioxamine mesylate or CoCl 2 treatment) (P < 0.05). The result of RNAi shows that the up-regulation of KDM6B is dependent on HIF-2α, but not on HIF-1α. The result of chromatin immunoprecipitation assay indicates that there is a hypoxia response element in KDM6B promoter (−4041 to −4037). The result of Co-IP assay indicates that KDM6B can form complex with HIF-2α or HIF-1α. The knockdown experiment implies that KDM6B is a potential regulator for HIF-2α target genes. These data demonstrate that KDM6B is a new hypoxia response gene regulated by HIF-2α. Our results also show that KDM6B is a potential coactivator of HIF-α, which is important for the activation of hypoxia response genes.

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Section: Discussionmentioning

confidence: 68%

Regulation of histone demethylase KDM6B by hypoxia-inducible factor-2α

Guo¹,

Tian²,

Wang³

et al. 2015

ABBS

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“…Our previous work with the TD model showed that upon C/EBP␣ induction, there is a gradual loss of H3K27me3 at C/EBP␣ binding sites, particularly at de novo enhancers that harbor high levels of H3K27me3 and low levels of H3K4me prior to induction (14 linked to active Pol II elongation (20,31,32), an event critical for the establishment of LTTM (Fig. 4A).…”

Section: Resultsmentioning

confidence: 95%

A Transcription Factor Pulse Can Prime Chromatin for Heritable Transcriptional Memory

Iberg-Badeaux

Collombet

Beaugerie

et al. 2017

Molecular and Cellular Biology

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Short-term and long-term transcriptional memory is the phenomenon whereby the kinetics or magnitude of gene induction is enhanced following a prior induction period. Short-term memory persists within one cell generation or in postmitotic cells, while long-term memory can survive multiple rounds of cell division. We have developed a tissue culture model to study the epigenetic basis for longterm transcriptional memory (LTTM) and subsequently used this model to better understand the epigenetic mechanisms that enable heritable memory of temporary stimuli. We find that a pulse of transcription factor CCAAT/enhancer-binding protein alpha (C/EBP␣) induces LTTM on a subset of target genes that survives nine cell divisions. The chromatin landscape at genes that acquire LTTM is more repressed than at those genes that do not exhibit memory, akin to a latent state. We show through chromatin immunoprecipitation (ChIP) and chemical inhibitor studies that RNA polymerase II (Pol II) elongation is important for establishing memory in this model but that Pol II itself is not retained as part of the memory mechanism. More generally, our work reveals that a transcription factor involved in lineage specification can induce LTTM and that failure to rerepress chromatin is one epigenetic mechanism underlying transcriptional memory.

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“…Moreover, removal of H3K27me3, an EED-binding target, will destabilize binding of PRC2 itself, potentially initiating a negative feedback loop augmented by the incurrence of symmetric H3K4me3 when transcription commences. Notably, JMJD3 has also been implicated in regulating the release of paused RNA Pol II into productive elongation, traveling along the gene body to clear H3K27me3 (Chen et al 2012;Estará s et al 2013). With respect to removal of PRC1 and deubiquitinylation of H2A, multiple proteins have been identified that possess deubiquitinylation activity toward H2A in mammals, including MYSM1, USP3, USP7, USP16, USP21, and USP22 (Weake and Workman 2008;Atanassov et al 2011).…”

Section: Resolution Of Bivalent Domains During Differentiationmentioning

confidence: 99%

A double take on bivalent promoters

2013

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Histone modifications and chromatin-associated protein complexes are crucially involved in the control of gene expression, supervising cell fate decisions and differentiation. Many promoters in embryonic stem (ES) cells harbor a distinctive histone modification signature that combines the activating histone H3 Lys 4 trimethylation (H3K4me3) mark and the repressive H3K27me3 mark. These bivalent domains are considered to poise expression of developmental genes, allowing timely activation while maintaining repression in the absence of differentiation signals. Recent advances shed light on the establishment and function of bivalent domains; however, their role in development remains controversial, not least because suitable genetic models to probe their function in developing organisms are missing. Here, we explore avenues to and from bivalency and propose that bivalent domains and associated chromatin-modifying complexes safeguard proper and robust differentiation.

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RNA polymerase II progression through H3K27me3-enriched gene bodies requires JMJD3 histone demethylase

Cited by 49 publications

References 44 publications

Regulation of histone demethylase KDM6B by hypoxia-inducible factor-2α

Regulation of histone demethylase KDM6B by hypoxia-inducible factor-2α

A Transcription Factor Pulse Can Prime Chromatin for Heritable Transcriptional Memory

A double take on bivalent promoters

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RNA polymerase II progression through H3K27me3-enriched gene bodies requires JMJD3 histone demethylase

Cited by 49 publications

References 44 publications

Regulation of histone demethylase KDM6B by hypoxia-inducible factor-2&alpha;

Regulation of histone demethylase KDM6B by hypoxia-inducible factor-2&alpha;

A Transcription Factor Pulse Can Prime Chromatin for Heritable Transcriptional Memory

A double take on bivalent promoters

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Resources

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Regulation of histone demethylase KDM6B by hypoxia-inducible factor-2α

Regulation of histone demethylase KDM6B by hypoxia-inducible factor-2α