This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Chernukhin, I.
Right arrow Articles by Klenova, E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chernukhin, I.
Right arrow Articles by Klenova, E.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, March 2007, p. 1631-1648, Vol. 27, No. 5
0270-7306/07/$08.00+0     doi:10.1128/MCB.01993-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

CTCF Interacts with and Recruits the Largest Subunit of RNA Polymerase II to CTCF Target Sites Genome-Wide{triangledown}

Igor Chernukhin,1,{dagger} Shaharum Shamsuddin,1,{dagger},{ddagger} Sung Yun Kang,1,{dagger} Rosita Bergström,2 Yoo-Wook Kwon,3 WenQiang Yu,2 Joanne Whitehead,2,§ Rituparna Mukhopadhyay,2 France Docquier,1 Dawn Farrar,1 Ian Morrison,1 Marc Vigneron,4 Shwu-Yuan Wu,5 Cheng-Ming Chiang,5 Dmitri Loukinov,3 Victor Lobanenkov,3 Rolf Ohlsson,2 and Elena Klenova1*

Department of Biological Sciences, University of Essex, Wivenhoe Park, Colchester, Essex CO4 3SQ, United Kingdom,1 Department of Development & Genetics, Evolution Biology Centre, Uppsala University, Norbyvägen 18A, S-752 36 Uppsala, Sweden,2 Molecular Pathology Section, LIP, NIAID, NIH, Building 7, Room 303, MSC-0760, Bethesda, Maryland 20892-0760,3 UMR 7175 CNRS-ULP, E.S.B.S., Boulevard Sébastien Brant, BP 10413, 67412 Illkirch Cedex,France,4 Department of Biochemistry, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106-49355

Received 24 October 2006/ Returned for modification 17 November 2006/ Accepted 18 December 2006

CTCF is a transcription factor with highly versatile functions ranging from gene activation and repression to the regulation of insulator function and imprinting. Although many of these functions rely on CTCF-DNA interactions, it is an emerging realization that CTCF-dependent molecular processes involve CTCF interactions with other proteins. In this study, we report the association of a subpopulation of CTCF with the RNA polymerase II (Pol II) protein complex. We identified the largest subunit of Pol II (LS Pol II) as a protein significantly colocalizing with CTCF in the nucleus and specifically interacting with CTCF in vivo and in vitro. The role of CTCF as a link between DNA and LS Pol II has been reinforced by the observation that the association of LS Pol II with CTCF target sites in vivo depends on intact CTCF binding sequences. "Serial" chromatin immunoprecipitation (ChIP) analysis revealed that both CTCF and LS Pol II were present at the ß-globin insulator in proliferating HD3 cells but not in differentiated globin synthesizing HD3 cells. Further, a single wild-type CTCF target site (N-Myc-CTCF), but not the mutant site deficient for CTCF binding, was sufficient to activate the transcription from the promoterless reporter gene in stably transfected cells. Finally, a ChIP-on-ChIP hybridization assay using microarrays of a library of CTCF target sites revealed that many intergenic CTCF target sequences interacted with both CTCF and LS Pol II. We discuss the possible implications of our observations with respect to plausible mechanisms of transcriptional regulation via a CTCF-mediated direct link of LS Pol II to the DNA.

* Corresponding author. Mailing address: Department of Biological Sciences, Central Campus, University of Essex, Wivenhoe Park, Colchester, Essex CO4 3SQ, United Kingdom. Phone: 44(0)1206-874868. Fax: 44(0)1206-872592. E-mail: klenovae{at}essex.ac.uk.

{triangledown} Published ahead of print on 8 January 2007.

{dagger} These authors contributed equally to this work.

{ddagger} Present address: School of Health Sciences, Universiti Sains Malaysia, Health Campus, 16150 Kubang Kerian, Kelantan, Malaysia.

§ Present address: Mechanics and Genetics of Embryonic and Tumoral Development, UMR 168 CNRS/Institut Curie, 75005 Paris, France.

Molecular and Cellular Biology, March 2007, p. 1631-1648, Vol. 27, No. 5
0270-7306/07/$08.00+0     doi:10.1128/MCB.01993-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Zlatanova, J., Caiafa, P. (2009). CTCF and its protein partners: divide and rule?. J. Cell Sci. 122: 1275-1284 [Abstract] [Full Text]  
  • Bowers, S. R., Mirabella, F., Calero-Nieto, F. J., Valeaux, S., Hadjur, S., Baxter, E. W., Merkenschlager, M., Cockerill, P. N. (2009). A Conserved Insulator That Recruits CTCF and Cohesin Exists between the Closely Related but Divergently Regulated Interleukin-3 and Granulocyte-Macrophage Colony-Stimulating Factor Genes. Mol. Cell. Biol. 29: 1682-1693 [Abstract] [Full Text]  
  • MacPherson, M. J., Beatty, L. G., Zhou, W., Du, M., Sadowski, P. D. (2009). The CTCF Insulator Protein Is Posttranslationally Modified by SUMO. Mol. Cell. Biol. 29: 714-725 [Abstract] [Full Text]  
  • Ribeiro de Almeida, C., Heath, H., Krpic, S., Dingjan, G. M., van Hamburg, J. P., Bergen, I., van de Nobelen, S., Sleutels, F., Grosveld, F., Galjart, N., Hendriks, R. W. (2009). Critical Role for the Transcription Regulator CCCTC-Binding Factor in the Control of Th2 Cytokine Expression. J. Immunol. 182: 999-1010 [Abstract] [Full Text]  
  • Brown, J. M., Green, J., das Neves, R. P., Wallace, H. A.C., Smith, A. J.H., Hughes, J., Gray, N., Taylor, S., Wood, W. G., Higgs, D. R., Iborra, F. J., Buckle, V. J. (2008). Association between active genes occurs at nuclear speckles and is modulated by chromatin environment. JCB 182: 1083-1097 [Abstract] [Full Text]  
  • Wan, L.-B., Pan, H., Hannenhalli, S., Cheng, Y., Ma, J., Fedoriw, A., Lobanenkov, V., Latham, K. E., Schultz, R. M., Bartolomei, M. S. (2008). Maternal depletion of CTCF reveals multiple functions during oocyte and preimplantation embryo development. Development 135: 2729-2738 [Abstract] [Full Text]  
  • Chadwick, B. P. (2008). DXZ4 chromatin adopts an opposing conformation to that of the surrounding chromosome and acquires a novel inactive X-specific role involving CTCF and antisense transcripts. Genome Res 18: 1259-1269 [Abstract] [Full Text]  
  • Fretz, J. A., Shevde, N. K., Singh, S., Darnay, B. G., Pike, J. W. (2008). Receptor Activator of Nuclear Factor-{kappa}B Ligand-Induced Nuclear Factor of Activated T Cells (C1) Autoregulates Its Own Expression in Osteoclasts and Mediates the Up-Regulation of Tartrate-Resistant Acid Phosphatase. Mol. Endocrinol. 22: 737-750 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»