Ribosomal RNA gene transcription mediated by the master genome regulator protein CCCTC-binding factor (CTCF) is negatively regulated by the condensin complex.

نویسندگان

  • Kaimeng Huang
  • Jinping Jia
  • Changwei Wu
  • Mingze Yao
  • Min Li
  • Jingji Jin
  • Cizhong Jiang
  • Yong Cai
  • Duanqing Pei
  • Guangjin Pan
  • Hongjie Yao
چکیده

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.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

CTCF Mediates the Cell-Type Specific Spatial Organization of the Kcnq5 Locus and the Local Gene Regulation

Chromatin loops play important roles in the dynamic spatial organization of genes in the nucleus. Growing evidence has revealed that the multivalent functional zinc finger protein CCCTC-binding factor (CTCF) is a master regulator of genome spatial organization, and mediates the ubiquitous chromatin loops within the genome. Using circular chromosome conformation capture (4C) methodology, we disc...

متن کامل

Architectural proteins CTCF and cohesin have distinct roles in modulating the higher order structure and expression of the CFTR locus

Higher order chromatin structures across the genome are maintained in part by the architectural proteins CCCTC binding factor (CTCF) and the cohesin complex, which co-localize at many sites across the genome. Here, we examine the role of these proteins in mediating chromatin structure at the cystic fibrosis transmembrane conductance regulator (CFTR) gene. CFTR encompasses nearly 200 kb flanked ...

متن کامل

Genome-wide studies of CCCTC-binding factor (CTCF) and cohesin provide insight into chromatin structure and regulation.

Eukaryotic genomes are organized into higher order chromatin architectures by protein-mediated long-range interactions in the nucleus. CCCTC-binding factor (CTCF), a sequence-specific transcription factor, serves as a chromatin organizer in building this complex chromatin structure by linking chromosomal domains. Recent genome-wide studies mapping the binding sites of CTCF and its interacting p...

متن کامل

In Silico Genome-Wide Screening for TnrA-Regulated Genes of Bacillus clausii

Bacillus clausii TnrA transcription factor is required for global nitrogen regulation. In order to obtain anoverview of gene regulation by TnrA in B. clausii KSMK16, the entire genome of B. clausii was screened forthe consensus sequence, 5’-TGTNAN7TNACA-3’ known as the TnrA box, and 13 transcription units werefound containing a putative TnrA box. The TnrA targets identified in...

متن کامل

CTCF: insights into insulator function during development.

The genome of higher eukaryotes exhibits a patchwork of inactive and active genes. The nuclear protein CCCTC-binding factor (CTCF) when bound to insulator sequences can prevent undesirable crosstalk between active and inactive genomic regions, and it can also shield particular genes from enhancer function, a role that has many applications in development. Exciting recent work has demonstrated r...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:
  • The Journal of biological chemistry

دوره 288 36  شماره 

صفحات  -

تاریخ انتشار 2013