title: Ribosomal RNA gene transcription mediated by the master genome regulator protein CCCTC-binding factor (CTCF) is negatively regulated by the condensin complex.
abstract: CCCTC-binding factor (CTCF) is a ubiquitously expressed "master weaver" and plays multiple functions in the genome, including transcriptional activation/repression, chromatin insulation, imprinting, X chromosome inactivation, and high-order chromatin organization. It has been shown that CTCF facilitates the recruitment of the upstream binding factor onto ribosomal DNA (rDNA) and regulates the local epigenetic state of rDNA repeats. However, the mechanism by which CTCF modulates rRNA gene transcription has not been well understood. Here we found that wild-type CTCF augments the pre-rRNA level, cell size, and cell growth in cervical cancer cells. In contrast, RNA interference-mediated knockdown of CTCF reduced pre-rRNA transcription. CTCF positively regulates rRNA gene transcription in a RNA polymerase I-dependent manner. We identified an RRGR motif as a putative nucleolar localization sequence in the C-terminal region of CTCF that is required for activating rRNA gene transcription. Using mass spectrometry, we identified SMC2 and SMC4, two subunits of condensin complexes that interact with CTCF. Condensin negatively regulates CTCF-mediated rRNA gene transcription. Knockdown of SMC2 expression significantly facilitates the loading of CTCF and the upstream binding factor onto the rDNA locus and increases histone acetylation across the rDNA locus. Taken together, our study suggests that condensin competes with CTCF in binding to a specific rDNA locus and negatively regulates CTCF-mediated rRNA gene transcription.
authors.affiliation: From the Key Laboratory of Regenerative Biology of the Chinese Academy of Sciences, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China,; the College of Life Science, Jilin University, Changchun, Jilin 130012, China, and.
authors.forename: Kaimeng
authors.initials: K
authors.lastname: Huang
authors.affiliation: From the Key Laboratory of Regenerative Biology of the Chinese Academy of Sciences, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
authors.forename: Jinping
authors.initials: J
authors.lastname: Jia
authors.affiliation: From the Key Laboratory of Regenerative Biology of the Chinese Academy of Sciences, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
authors.forename: Changwei
authors.initials: C
authors.lastname: Wu
authors.affiliation: From the Key Laboratory of Regenerative Biology of the Chinese Academy of Sciences, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
authors.forename: Mingze
authors.initials: M
authors.lastname: Yao
authors.affiliation: the School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.affiliation: the College of Life Science, Jilin University, Changchun, Jilin 130012, China, and.
authors.forename: Jingji
authors.initials: J
authors.lastname: Jin
authors.affiliation: the School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
authors.forename: Cizhong
authors.initials: C
authors.lastname: Jiang
authors.affiliation: the College of Life Science, Jilin University, Changchun, Jilin 130012, China, and.
authors.forename: Yong
authors.initials: Y
authors.lastname: Cai
authors.affiliation: From the Key Laboratory of Regenerative Biology of the Chinese Academy of Sciences, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
authors.forename: Duanqing
authors.initials: D
authors.lastname: Pei
authors.affiliation: From the Key Laboratory of Regenerative Biology of the Chinese Academy of Sciences, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China,. Electronic address: pan_guangjin@gibh.ac.cn.
authors.forename: Guangjin
authors.initials: G
authors.lastname: Pan
authors.affiliation: From the Key Laboratory of Regenerative Biology of the Chinese Academy of Sciences, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China,. Electronic address: pan_guangjin@gibh.ac.cn.
authors.forename: Hongjie
authors.initials: H
authors.lastname: Yao
mesh_terms: D000107:Acetylation; D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D000076246:CCCTC-Binding Factor; D004275:DNA, Ribosomal / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D020459:Genes, rRNA / Q000502:physiology*; D056426:Genetic Loci / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D012318:RNA Polymerase I / Q000235:genetics / Q000378:metabolism*; D012322:RNA Precursors / Q000096:biosynthesis* / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D061785:Transcription Initiation, Genetic / Q000502:physiology*
chemical_list: D000076246:CCCTC-Binding Factor; C000619697:CTCF protein, human; D004275:DNA, Ribosomal; D004268:DNA-Binding Proteins; D046912:Multiprotein Complexes; D012322:RNA Precursors; D012097:Repressor Proteins; C108312:condensin complexes; D012318:RNA Polymerase I; D000251:Adenosine Triphosphatases
keywords: Chromosomes/Non-histone Chromosomal Proteins; Histone Modification; RNA Interference (RNAi); RNA Polymerase I; Ribosomal RNA (rRNA)