The chromatin remodeler RSF1 controls centromeric histone modifications to coordinate chromosome segregation

Lee, Ho Soo; Lin, Zhonghui; Chae, Sunyoung; Yoo, Young Suk; Kim, Byung Gyu; Lee, Youngsoo; Johnson, Jared L.; Kim, You Sun; Cantley, Lewis C.; Lee, Chang Woo; Yu, Hongtao; Cho, Hyeseong

doi:10.1038/s41467-018-06377-w

Cited by 22 publications

(24 citation statements)

References 47 publications

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“…Some of these MeDEGs are involved in tumorigenesis. For instance, SGOL1, a member of the shugoshin family of proteins, is thought to protect centromeric cohesion during mitosis, and its dysregulation at centromeres can lead to chromosome missegregation and miotic arrest [40, 41]. Mu et al found that SGOL1 expression levels are higher in prostate cancer tissues, and SGLO1 knockdown results in the inhibition of tumor cell proliferation, migration, and invasion [42].…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of DNA methylation and gene expression profiles in cholangiocarcinoma

Zhang

Meng

et al. 2019

Cancer Cell Int

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Background: The incidence of cholangiocarcinoma (CCA) has risen in recent years, and it has become a significant health burden worldwide. However, the mechanisms underlying tumorigenesis and progression of this disease remain largely unknown. An increasing number of studies have demonstrated crucial biological functions of epigenetic modifications, especially DNA methylation, in CCA. The present study aimed to identify and analyze methylationregulated differentially expressed genes (MeDEGs) involved in CCA tumorigenesis and progression by bioinformatics analysis. Methods:The gene expression profiling dataset (GSE119336) and gene methylation profiling dataset (GSE38860) were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) and differentially methylated genes (DMGs) were identified using the limma packages of R and GEO2R, respectively. The MeDEGs were obtained by overlapping the DEGs and DMGs. Functional enrichment analyses of these genes were then carried out. Protein-protein interaction (PPI) networks were constructed using STRING and visualized in Cytoscape to determine hub genes. Finally, the results were verified based on The Cancer Genome Atlas (TCGA) database. Results:We identified 98 hypermethylated, downregulated genes and 93 hypomethylated, upregulated genes after overlapping the DEGs and DMGs. These genes were mainly enriched in the biological processes of the cell cycle, nuclear division, xenobiotic metabolism, drug catabolism, and negative regulation of proteolysis. The top nine hub genes of the PPI network were F2, AHSG, RRM2, AURKB, CCNA2, TOP2A, BIRC5, PLK1, and ASPM. Moreover, the expression and methylation status of the hub genes were significantly altered in TCGA. Conclusions:Our study identified novel methylation-regulated differentially expressed genes (MeDEGs) and explored their related pathways and functions in CCA, which may provide novel insights into a further understanding of methylation-mediated regulatory mechanisms in CCA.

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Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of DNA methylation and gene expression profiles in cholangiocarcinoma

Zhang

Meng

et al. 2019

Cancer Cell Int

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“…Centromeric HDAC1, H2A-pT120 and Sog1 localization was restored in RSF1-KO cells expressing the C-terminal region (aa 627–1441) or C-terminal region (aa 982–1441). All the results imply that the C-terminal region (aa 627–1441) or C-terminal region (aa 982–1441) of RSF1 can interact with and recruit HDAC1 to centromeres to maintain centromere cohesion [ 45 ] (Fig. 3 h).…”

Section: Rsf1 Interacts With and Recruits Hdac1 To Centromeres To Protect Centromeric Cohesionmentioning

confidence: 99%

RSF1 in cancer: interactions and functions

2021

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RSF1, remodelling and spacing factor 1, is an important interphase centromere protein and is overexpressed in many types of cancers and correlated with poor overall survival. RSF1 has functions mainly in maintaining chromosome stability, facilitating DNA repair, maintaining the protein homeostasis of RSF1 and suppressing the transcription of some oncogenes when RSF1 protein is expressed at an optimal level; however, RSF1 overexpression facilitates drug resistance and cell cycle checkpoint inhibition to prompt cancer proliferation and survival. The RSF1 expression level and gene background are crucial for RSF1 functions, which may explain why RSF1 has different functions in different cancer types. This review summarizes the functional domains of RSF1, the overexpression status of RSF1 and SNF2H in cancer based on the TCGA and GTEX databases, the cancer-related functions of RSF1 in interacting with H2Aub, HDAC1, CENP-A, PLK1, ATM, CENP-S, SNF2H, HBX, BubR1, cyclin E1, CBP and NF-κB and the potential clinical value of RSF1, which will lay a theoretical foundation for the structural biology study of RSF1 and application of RSF1 inhibitors, truncated RSF1 proteins and SNF2H inhibitors in the treatment of RSF1-overexpressing tumours.

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“…In this regard, the mitotic role of Remodeling and spacing factor1 (RSF1), a member of the ISWI family of ATPases, is informative. Like ARID2, RSF1 is required for the centromeric deposition of PLK1 45 and promotes centromeric H2AT120P 46 . The latter activity is achieved by suppressing H2A acetylation.…”

Section: Main Textmentioning

confidence: 99%

Mammalian SWI/SNF chromatin remodeler is essential for reductional meiosis in males

Menon

Magnuson

2020

Preprint

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9BRG1, a catalytic subunit of the mammalian SWI/SNF nucleosome remodeler is essential for 10 male meiosis 1 . In addition to BRG1, multiple subunits (~10-14) some of which are mutually 11 exclusive, constitute biochemically distinct SWI/SNF subcomplexes, whose functions in 12 gametogenesis remain unknown. Here, we identify a role for the PBAF (Polybromo -Brg1 13Associated Factor) complex in the regulation of meiotic cell division. The germ cell-specific 14 depletion of PBAF specific subunit, ARID2 resulted in a metaphase-I arrest. Arid2 cKO metaphase-15 I spermatocytes displayed defects in chromosome organization and spindle assembly. 16Additionally, mutant centromeres were devoid of Polo-like kinase1 (PLK1), a known regulator of 17 the spindle assembly checkpoint (SAC) 2 . The loss of PLK1 coincided with an abnormal 18 chromosome-wide expansion of centromeric chromatin modifications such as Histone H3 19 threonine3 phosphorylation (H3T3P) and Histone H2A threonine120 phosphorylation 20 (H2AT120P) that are critical for chromosome segregation 3,4 . Consistent with the known role of 21 these histone modifications in chromosome passenger complex (CPC) recruitment, Arid2 cKO 22 metaphase-I chromosomes display defects in CPC association. We propose that ARID2 facilitates 23 metaphase-I exit by regulating spindle assembly and centromeric chromatin. 25Keywords: PBAF remodeler, ARID2, male reductional meiosis, spindle assembly, H3T3P, 26 H2AT120P 27 28 1 Main text: 29We previously demonstrated a role for the mammalian SWI/SNF chromatin remodeling complex 30 in meiotic progression by conditionally ablating its ATPase subunit, BRG1, in the testis 1,5 . Given 31 that SWI/SNF complexes are biochemically heterogenous 6,7 , it is possible that certain 32 subcomplexes might selectively govern distinct spermatogenic processes. To address this 33 possibility, we examined existing RNA-seq data generated from purified spermatogenic cell 34 populations 8 and monitored the temporal expression profiles of SWI/SNF subunits that define two 35 subcomplexes, namely, BAF (Brg1 Associated Factor) and PBAF (Polybromo-BAF) ( Fig. 1a). Of 36 particular interest were the ARID (AT-rich interaction domain) containing SWI/SNF subunits, 37 known to bind DNA with loose specificity 9 . Among the subunits examined, the mRNA expression 38 of PBAF DNA binding subunit 10 , Arid2, drew our attention as it peaked at pachynema ( Fig. 1a). 39More recent single cell RNA seq data also identified Arid2 as an early pachytene marker 11 , 40 suggesting a role in meiosis-I. We therefore performed immunostaining on testes cryosections 41 to profile ARID2 abundance in prophase-I spermatocytes staged by γH2Ax. Consistent with its 42 mRNA profile, ARID2 went from being undetectable to expressed weakly, during the transition 43 from pre-leptonema to zygonema, but appeared elevated at pachynema which is distinguished 44 by the sex body 12 . Additionally, ARID2 was also detected in round spermatids, enriched proximally 45 to chromocenters (Fig. 1b). To investigate its rol...

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The chromatin remodeler RSF1 controls centromeric histone modifications to coordinate chromosome segregation

Cited by 22 publications

References 47 publications

Comprehensive analysis of DNA methylation and gene expression profiles in cholangiocarcinoma

Comprehensive analysis of DNA methylation and gene expression profiles in cholangiocarcinoma

RSF1 in cancer: interactions and functions

Mammalian SWI/SNF chromatin remodeler is essential for reductional meiosis in males

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