The chromatin remodeller RSF1 is essential for PLK1 deposition and function at mitotic kinetochores

Lee, Ho-Soo; Park, Yong-Yea; Cho, Young Min; Chae, Sunyoung; Yoo, Young-Suk; Kwon, Myung-Hee; Lee, Chang-Woo; Cho, Hyeseong

doi:10.1038/ncomms8904

Cited by 28 publications

(26 citation statements)

References 50 publications

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“…In this study, we demonstrated that circMRPS35 participated in chromatin remodeling and increased H4K5 acetylation associated with target genes promoters, which reveals a novel mechanism of circRNA. Chromatin remodeling is the dynamic modification of chromatin structure to allow regulatory elements access to condensed genomic DNA, thus altering gene expression [32]. Studies have mainly focused on the role of protein complexes in chromatin remodeling, including histone modifying enzymes, DNA modifying enzymes and ATP-dependent chromatin remodeling complexes [33,34].…”

Section: Discussionmentioning

confidence: 99%

CircMRPS35 suppresses gastric cancer progression via recruiting KAT7 to govern histone modification

et al. 2020

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Background: Aberrant expression of circular RNAs contributes to the initiation and progression of cancers, but the underlying mechanism remains elusive. Methods: RNA-seq and qRT-PCR were performed to screen differential expressed circRNAs between gastric cancer tissues and adjacent normal tissues. Candidate circRNA (circMRPS35) was screened out and validated by qRT-PCR. Cell proliferation and invasion ability were determined by CCK-8 and cell invasion assays. RNA-seq, GO-pathway, RNA pull-down and ChIRP were further applied to search for detailed mechanism. Results: Here, a novel circRNA named circMRPS35, was screened out by RNA-seq in gastric cancer tissues, whose expression is related to clinicopathological characteristics and prognosis in gastric cancer patients. Biologically, circMRPS35 suppresses the proliferation and invasion of gastric cancer cells in vitro and in vivo. Mechanistically, circMRPS35 acts as a modular scaffold to recruit histone acetyltransferase KAT7 to the promoters of FOXO1 and FOXO3a genes, which elicits acetylation of H4K5 in their promoters. Particularly, circMRPS35 specifically binds to FOXO1/3a promoter regions directly. Thus, it dramatically activates the transcription of FOXO1/3a and triggers subsequent response of their downstream target genes expression, including p21, p27, Twist1 and E-cadherin, resulting in the inhibition of cell proliferation and invasion. Moreover, circMRPS35 expression positively correlates with that of FOXO1/3a in gastric cancer tissues. Conclusions: Our findings not only reveal the pivotal roles of circMRPS35 in governing histone modification in anticancer treatment, but also advocate for triggering circMRPS35/KAT7/FOXO1/3a pathway to combat gastric cancer.

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Section: Discussionmentioning

confidence: 99%

CircMRPS35 suppresses gastric cancer progression via recruiting KAT7 to govern histone modification

et al. 2020

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“…Subsequently, the RSF complex is shown to generate regularly spaced nucleosomes from irregularly spaced nucleosomes (23). However, aside from the evidence that RSF1 helps load proteins onto centromeres and at the sites of DNA damage (43)(44)(45)(46), the function of RSF1 on chromatin in general remains largely unknown. Our preliminary studies of in vitro transcription revealed that the presence of RSF1 represses transcription activation of H2Aub-containing chromatin, but not chromatin-containing H2A.…”

Section: Discussionmentioning

confidence: 99%

Role of remodeling and spacing factor 1 in histone H2A ubiquitination-mediated gene silencing

Zhang

Jones

et al. 2017

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

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Posttranslational histone modifications play important roles in regulating chromatin-based nuclear processes. Histone H2AK119 ubiquitination (H2Aub) is a prevalent modification and has been primarily linked to gene silencing. However, the underlying mechanism remains largely obscure. Here we report the identification of RSF1 (remodeling and spacing factor 1), a subunit of the RSF complex, as a H2Aub binding protein, which mediates the gene-silencing function of this histone modification. RSF1 associates specifically with H2Aub, but not H2Bub nucleosomes, through a previously uncharacterized and obligatory region designated as ubiquitinated H2A binding domain. In human and mouse cells, genes regulated by RSF1 overlap significantly with those controlled by RNF2/Ring1B, the subunit of Polycomb repressive complex 1 (PRC1) which catalyzes the ubiquitination of H2AK119. About 82% of H2Aub-enriched genes, including the classic PRC1 target genes, are bound by RSF1 around their transcription start sites. Depletion of H2Aub levels by Ring1B knockout results in a significant reduction of RSF1 binding. In contrast, RSF1 knockout does not affect RNF2/Ring1B or H2Aub levels but leads to derepression of H2Aub target genes, accompanied by changes in H2Aub chromatin organization and release of linker histone H1. The action of RSF1 in H2Aub-mediated gene silencing is further demonstrated by chromatin-based in vitro transcription. Finally, RSF1 and Ring1 act cooperatively to regulate mesodermal cell specification and gastrulation during early embryonic development. Taken together, these data identify RSF1 as a H2Aub reader that contributes to H2Aub-mediated gene silencing by maintaining a stable nucleosome pattern at promoter regions.

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“…For example, RSF1 directly binds to PLK1 to play an important role in PLK1 deposition and function at mitotic kinetochores [64]; PLK1 phosphorylates PAX3-FOXO1 to stabilize the protein and has been proposed as a rational target for treating alveolar rhabdomyosarcoma [65]; CLIP-170 recruits PLK1 to kinetochores during early mitosis for chromosome alignment [66]. Among the interactive partners with PLK1 , tumor suppressor genes are noteworthy considering the oncogenic role of PLK1 in human cancers.…”

Section: Plk1 and Human Cancermentioning

confidence: 99%

PLK1, A Potential Target for Cancer Therapy

Liu

Sun

Wang

2017

Translational Oncology

347

269

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Polo-like kinase 1 (PLK1) plays an important role in the initiation, maintenance, and completion of mitosis. Dysfunction of PLK1 may promote cancerous transformation and drive its progression. PLK1 overexpression has been found in a variety of human cancers and was associated with poor prognoses in cancers. Many studies have showed that inhibition of PLK1 could lead to death of cancer cells by interfering with multiple stages of mitosis. Thus, PLK1 is expected to be a potential target for cancer therapy. In this article, we examined PLK1’s structural characteristics, its regulatory roles in cell mitosis, PLK1 expression, and its association with survival prognoses of cancer patients in a wide variety of cancer types, PLK1 interaction networks, and PLK1 inhibitors under investigation. Finally, we discussed the key issues in the development of PLK1-targeted cancer therapy.

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The chromatin remodeller RSF1 is essential for PLK1 deposition and function at mitotic kinetochores

Cited by 28 publications

References 50 publications

CircMRPS35 suppresses gastric cancer progression via recruiting KAT7 to govern histone modification

CircMRPS35 suppresses gastric cancer progression via recruiting KAT7 to govern histone modification

Role of remodeling and spacing factor 1 in histone H2A ubiquitination-mediated gene silencing

PLK1, A Potential Target for Cancer Therapy

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