Ribosomal RNA Gene Transcription Mediated by the Master Genome Regulator Protein CCCTC-binding Factor (CTCF) Is Negatively Regulated by the Condensin Complex

Huang, Kainian; Jia, Jinping; Wu, Changwei; Yao, Maojin; Li, Min; Jin, Jingji; Jiang, Cizhong; Cai, Yong; Pei, Duanqing; Pan, Guangjin; Yao, Hongjie

doi:10.1074/jbc.m113.486175

Cited by 48 publications

(43 citation statements)

References 48 publications

(55 reference statements)

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“…SMC4 has been implicated in colorectal, liver, and breast cancer (45-47), but has not been studied in prostate cancer or implicated in the metastatic cascade. In addition, SMC4/condensin interacts with the genomic transcriptional insulator CTCF, and thus may be required for oncogenic gene silencing (48). SQLE is a cholesterol biosynthesis enzyme that has been implicated in several cancers other than prostate, and, interestingly, is located in the chromosome 8q24 Myc oncogene amplicon (49)(50)(51).…”

Section: Discussionmentioning

confidence: 99%

The Landscape of Prognostic Outlier Genes in High-Risk Prostate Cancer

Zhao

Evans

Kothari

et al. 2016

Clinical Cancer Research

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Purpose: There is a clear need to improve risk stratification and to identify novel therapeutic targets in aggressive prostate cancer. The goal of this study was to investigate genes with outlier expression with prognostic association in high-risk prostate cancer patients as potential biomarkers and drug targets.Experimental Design: We interrogated microarray gene expression data from prostatectomy samples from 545 high-risk prostate cancer patients with long-term follow-up (mean 13.4 years). Three independent clinical datasets totaling an additional 545 patients were used for validation. Novel prognostic outlier genes were interrogated for impact on oncogenic phenotypes in vitro using siRNA-based knockdown. Association with clinical outcomes and comparison with existing prognostic instruments was assessed with multivariable models using a prognostic outlier score.Results: Analysis of the discovery cohort identified 20 prognostic outlier genes. Three top prognostic outlier genes were novel prostate cancer genes; NVL, SMC4, or SQLE knockdown reduced migration and/or invasion and outlier expression was significantly associated with poor prognosis. Increased prognostic outlier score was significantly associated with poor prognosis independent of standard clinicopathologic variables. Finally, the prognostic outlier score prognostic association is independent of, and adds to existing genomic and clinical tools for prognostication in prostate cancer (Decipher, the cell-cycle progression signature, and CAPRA-S).Conclusions: To our knowledge, this study represents the first unbiased high-throughput investigation of prognostic outlier genes in prostate cancer and demonstrates the potential biomarker and therapeutic importance of this previously unstudied class of cancer genes.

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Section: Discussionmentioning

confidence: 99%

The Landscape of Prognostic Outlier Genes in High-Risk Prostate Cancer

Zhao

Evans

Kothari

et al. 2016

Clinical Cancer Research

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“…Consistent with data from yeast system studies, the findings of several reports support the implication of mammalian condensin in regulating rDNA silencing. For example, the loss of the catalytic subunit of the condensin complex SMC2 significantly increases CTCF (CCCTC-binding factor)-mediated rDNA transcription (137). Data from chromatin immunoprecipitation (ChIP) analyses suggest that SMC2 more preferentially binds to the promoter and to transcribed regions than to nontranscribed regions of the human rDNA locus, and an SMC2 knockout increases UBF recruitment and enhances H4 acetylation enrichment around the rDNA promoter (137).…”

Section: Condensinsmentioning

confidence: 99%

“…Data from chromatin immunoprecipitation (ChIP) analyses suggest that SMC2 more preferentially binds to the promoter and to transcribed regions than to nontranscribed regions of the human rDNA locus, and an SMC2 knockout increases UBF recruitment and enhances H4 acetylation enrichment around the rDNA promoter (137). CTCF repression also increases SMC4 binding preferentially to the transcription initiation region and transcribed region of the rDNA locus (137). In SMC-depleted HeLa cells, sister NORs missegregate or segregate with a substantial delay, suggesting the structural instability of rDNA due to condensin depletion (138).…”

Section: Condensinsmentioning

confidence: 99%

“…For example, the loss of the catalytic subunit of the condensin complex SMC2 significantly increases CTCF (CCCTC-binding factor)-mediated rDNA transcription (137). Data from chromatin immunoprecipitation (ChIP) analyses suggest that SMC2 more preferentially binds to the promoter and to transcribed regions than to nontranscribed regions of the human rDNA locus, and an SMC2 knockout increases UBF recruitment and enhances H4 acetylation enrichment around the rDNA promoter (137). CTCF repression also increases SMC4 binding preferentially to the transcription initiation region and transcribed region of the rDNA locus (137).…”

Section: Condensinsmentioning

confidence: 99%

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The Epigenetic Pathways to Ribosomal DNA Silencing

Srivastava

Ahn

2016

Microbiol Mol Biol Rev

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SUMMARYHeterochromatin is the transcriptionally repressed portion of eukaryotic chromatin that maintains a condensed appearance throughout the cell cycle. At sites of ribosomal DNA (rDNA) heterochromatin, epigenetic states contribute to gene silencing and genome stability, which are required for proper chromosome segregation and a normal life span. Here, we focus on recent advances in the epigenetic regulation of rDNA silencing inSaccharomyces cerevisiaeand in mammals, including regulation by several histone modifications and several protein components associated with the inner nuclear membrane within the nucleolus. Finally, we discuss the perturbations of rDNA epigenetic pathways in regulating cellular aging and in causing various types of diseases.

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“…Recently, Huang et al (2013) reported that ectopically expressed CTCF promotes cell proliferation in a cell line of cervical cancer cells (HeLa-S3), suggesting that CTCF is an oncogene rather than a tumor suppressor in cervical cancer cells.…”

Section: Discussionmentioning

confidence: 99%

BORIS and CTCF are overexpressed in squamous intraepithelial lesions and cervical cancer

Velázquez-Hernández¹,

Reyes-Romero²,

Barragán-Hernández³

et al. 2015

Genet. Mol. Res.

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ABSTRACT. We investigated the expression of Brother of Regulator of Imprinted Sites (BORIS) and CCCTC-binding factor (CTCF) in squamous intraepithelial lesions and cervical cancer. To analyze BORIS and CTCF expression, an endocervical cytobrush sample was taken for total RNA isolation. CTCF and BORIS mRNA was quantified from total RNA using quantitative reverse transcription-polymerase chain reaction. A total of 71 samples were collected and classified according to the Bethesda Classification of squamous intraepithelial lesions. BORIS 6095 BORIS and CTCF expression in cervical dysplasia and cancer ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (2): 6094-6100 (2015) expression was observed in 9 (12.7%) samples; of these, 5.3, 5.9, 14.8, and 37.5% in the groups that were cytology negative for intraepithelial lesion or malignancy, low-grade squamous intraepithelial lesions (LSIL), highgrade squamous intraepithelial lesions (HSIL), and invasive cervical carcinoma, respectively. The expression level of BORIS was significantly higher in the group with invasive cervical carcinoma as compared with the groups negative for intraepithelial lesion or malignancy, LSIL, and HSIL (P < 0.0005). CTCF mRNA was expressed in all samples. CTCF expression was significantly higher in carcinoma groups compared with LSIL, HSIL, and negative for intraepithelial lesion or malignancy groups. We found that BORIS and CTCF expressions in the LSIL and invasive cervical carcinoma groups were higher than expression in cytological normal samples. Additional studies should be conducted to examine the function of transcription factors during different stages of the transformation of cervical cancer cells.

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Ribosomal RNA Gene Transcription Mediated by the Master Genome Regulator Protein CCCTC-binding Factor (CTCF) Is Negatively Regulated by the Condensin Complex

Cited by 48 publications

References 48 publications

The Landscape of Prognostic Outlier Genes in High-Risk Prostate Cancer

The Landscape of Prognostic Outlier Genes in High-Risk Prostate Cancer

The Epigenetic Pathways to Ribosomal DNA Silencing

BORIS and CTCF are overexpressed in squamous intraepithelial lesions and cervical cancer

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