ESET methylates UBF at K232/254 and regulates nucleolar heterochromatin plasticity and rDNA transcription

Hwang, Yu Jin; Han, Dohyun; Kim, Ki Yoon; Min, Sun‐Joon; Kowall, Neil W.; Yang, Liu; Lee, Jung‐Hee; Kim, Youngsoo; Ryu, Hoon

doi:10.1093/nar/gkt1041

Cited by 27 publications

(15 citation statements)

References 40 publications

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“…Several studies have identified Setdb1 in the cytoplasm [ 19 ] and its cytoplasmic methyltransferase activity was demonstrated both in mammals [ 46 ] and C. elegans [ 47 ]. Furthermore, Setdb1 binds several non-histone proteins in the nucleus [ 22 , 67 ] and can also methylate some of them [ 68 , 69 ]. It is tempting to speculate that the relocalisation of Setdb1 to the cytoplasm could also lead to methylation of non-histone proteins in the cytoplasm.…”

Section: Discussionmentioning

confidence: 99%

Canonical Wnt signalling regulates nuclear export of Setdb1 during skeletal muscle terminal differentiation

et al. 2016

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The histone 3 lysine 9 methyltransferase Setdb1 is essential for both stem cell pluripotency and terminal differentiation of different cell types. To shed light on the roles of Setdb1 in these mutually exclusive processes, we used mouse skeletal myoblasts as a model of terminal differentiation. Ex vivo studies on isolated single myofibres showed that Setdb1 is required for adult muscle stem cells expansion following activation. In vitro studies in skeletal myoblasts confirmed that Setdb1 suppresses terminal differentiation. Genomic binding analyses showed a release of Setdb1 from selected target genes upon myoblast terminal differentiation, concomitant to a nuclear export of Setdb1 to the cytoplasm. Both genomic release and cytoplasmic Setdb1 relocalisation during differentiation were dependent on canonical Wnt signalling. Transcriptomic assays in myoblasts unravelled a significant overlap between Setdb1 and Wnt3a regulated genetic programmes. Together, our findings revealed Wnt-dependent subcellular relocalisation of Setdb1 as a novel mechanism regulating Setdb1 functions and myogenesis.

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Section: Discussionmentioning

confidence: 99%

Canonical Wnt signalling regulates nuclear export of Setdb1 during skeletal muscle terminal differentiation

et al. 2016

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“…AGO2 is present in both the cytoplasm and the nucleus ( 65 ). SETDB1 functions mainly in the nucleus but can also localize in the cytoplasm, depending on the type of cells ( 51 , 66 ). As shown in Figure 3D , AR agRNA-bound AGO2 was localized at the promoter even in the absence of SETDB1 with AGO2 alone remaining and the AR promoter still active (Figure 1C ), suggesting that AGO2 arrives first and then recruits nuclear SETDB1.…”

Section: Resultsmentioning

confidence: 99%

AGO2 and SETDB1 cooperate in promoter-targeted transcriptional silencing of the androgen receptor gene

Cho

Park

Kang

2014

Nucleic Acids Research

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In mammals, RNA interference is primarily a post-transcriptional mechanism. Evidence has accumulated for additional role in transcriptional gene silencing (TGS) but the question for a good paradigm for small interfering antigene RNA (agRNA)-induced chromatin modification remains unanswered. Here, we show that SETDB1, a histone H3-lysine 9 (H3K9)-specific methyltransferase, cooperates with Argonaute-2 (AGO2) and plays an essential role in agRNA-induced TGS. The androgen receptor (AR) gene was transcriptionally silenced by agRNA targeted to its promoter, and we show that this repression was mitigated by knockdown of SETDB1 or AGO2. Chromatin immunoprecipitation demonstrated that agRNA-driven AGO2 was first targeted to the AR promoter, followed by SETDB1. SIN3A and HDAC1/2, the components of the SIN3-HDAC complex, immunoprecipitated with SETDB1, and localized at the agRNA-targeted promoter. Agreeing with the presence of SETDB1, trimethyl-H3K9 was enriched in the AR promoter. Both EZH2 and trimethyl-H3K27 were also present in the targeted locus; accordingly, EZH2 immunoprecipitated with SETDB1. DNA methylation level was not significantly changed, suggesting the absence of de novo methylating activity in agRNA-induced AR promoter. Our results demonstrate that SETDB1, together with AGO2, plays an essential role in TGS through recruiting chromatin remodeler and/or other modifiers, consequently creating a repressive chromatin milieu at the targeted promoter.

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“…Whereas SUV39H1 is targeted to rDNA genes (together with sirtuin 1, as part of the energy-dependent nucleolar silencing complex) to methylate H3K9 (REF. 78), SETDB1 negatively regulates rDNA transcription by methylating one of the major nucleolar transcription factors, upstream-binding factor 1 (UBF1; also known as nucleolar transcription factor 1) 104 .…”

Section: Gene Silencingmentioning

confidence: 99%

Sound of silence: the properties and functions of repressive Lys methyltransferases

Mozzetta¹,

Boyarchuk²,

Pontis³

et al. 2015

Nat Rev Mol Cell Biol

163

162

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The methylation of histone Lys residues by Lys methyltransferases (KMTs) regulates chromatin organization and either activates or represses gene expression, depending on the residue that is targeted. KMTs are emerging as key components in several cellular processes, and their deregulation is often associated with pathogenesis. Here, we review the current knowledge on the main KMTs that are associated with gene silencing: namely, those responsible for methylating histone H3 Lys 9 (H3K9), H3K27 and H4K20. We discuss their biochemical properties and the various mechanisms by which they are targeted to the chromatin and regulate gene expression, as well as new data on the interplay between them and other chromatin modifiers.

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ESET methylates UBF at K232/254 and regulates nucleolar heterochromatin plasticity and rDNA transcription

Cited by 27 publications

References 40 publications

Canonical Wnt signalling regulates nuclear export of Setdb1 during skeletal muscle terminal differentiation

Canonical Wnt signalling regulates nuclear export of Setdb1 during skeletal muscle terminal differentiation

AGO2 and SETDB1 cooperate in promoter-targeted transcriptional silencing of the androgen receptor gene

Sound of silence: the properties and functions of repressive Lys methyltransferases

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