%0 Journal Article %1 ISI:000308959800019 %A Junier, Ivan %A Dale, Ryan K. %A Hou, Chunhui %A Kepes, Francois %A Dean, Ann %C GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND %D 2012 %I OXFORD UNIV PRESS %J NUCLEIC ACIDS RESEARCH %K imported iscpif %N 16 %P 7718-7727 %R 10.1093/nar/gks536 %T CTCF-mediated transcriptional regulation through cell type-specific chromosome organization in the beta-globin locus %V 40 %X The principles underlying the architectural landscape of chromatin beyond the nucleosome level in living cells remains largely unknown despite its potential to play a role in mammalian gene regulation. We investigated the three-dimensional folding of a 1 Mbp region of human chromosome 11 containing the beta-globin genes by integrating looping interactions of the CCCTC-binding insulator protein CTCF determined comprehensively by chromosome conformation capture (3C) into a polymer model of chromatin. We find that CTCF-mediated cell type-specific interactions in erythroid cells are organized to favor contacts known to occur in vivo between the beta-globin locus control region (LCR) and genes. In these cells, the modeled beta-globin domain folds into a globule with the LCR and the active globin genes on the periphery. In contrast, in non-erythroid cells, the globule is less compact with few but dominant CTCF interactions driving the genes away from the LCR. This leads to a decrease in contact frequencies that can exceed 1000-fold depending on the stiffness of the chromatin and the exact position of the genes. Our findings show that an ensemble of CTCF contacts functionally affects spatial distances between control elements and target genes contributing to chromosomal organization required for transcription.

@article{ISI:000308959800019, abstract = {{The principles underlying the architectural landscape of chromatin beyond the nucleosome level in living cells remains largely unknown despite its potential to play a role in mammalian gene regulation. We investigated the three-dimensional folding of a 1 Mbp region of human chromosome 11 containing the beta-globin genes by integrating looping interactions of the CCCTC-binding insulator protein CTCF determined comprehensively by chromosome conformation capture (3C) into a polymer model of chromatin. We find that CTCF-mediated cell type-specific interactions in erythroid cells are organized to favor contacts known to occur in vivo between the beta-globin locus control region (LCR) and genes. In these cells, the modeled beta-globin domain folds into a globule with the LCR and the active globin genes on the periphery. In contrast, in non-erythroid cells, the globule is less compact with few but dominant CTCF interactions driving the genes away from the LCR. This leads to a decrease in contact frequencies that can exceed 1000-fold depending on the stiffness of the chromatin and the exact position of the genes. Our findings show that an ensemble of CTCF contacts functionally affects spatial distances between control elements and target genes contributing to chromosomal organization required for transcription.}}, added-at = {2015-05-15T21:46:32.000+0200}, address = {{GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND}}, affiliation = {{Junier, I (Reprint Author), Univ Evry, Epigenom Project, 5 Rue Henri Desbrueres, F-91030 Evry, France. Junier, Ivan; Kepes, Francois, Univ Evry, Epigenom Project, F-91030 Evry, France. Junier, Ivan; Kepes, Francois, Univ Evry, CNRS, Genopole, Inst Syst \& Synthet Biol, F-91030 Evry, France. Junier, Ivan, Inst Complex Syst, Paris, France. Junier, Ivan, Ctr Genom Regulat, Barcelona 08003, Spain. Dale, Ryan K.; Hou, Chunhui; Dean, Ann, NIDDKD, Lab Cellular \& Dev Biol, NIH, Bethesda, MD 20892 USA.}}, author = {Junier, Ivan and Dale, Ryan K. and Hou, Chunhui and Kepes, Francois and Dean, Ann}, author-email = {{i.junier@gmail.com francois.kepes@epigenomique.genopole.fr anndean@helix.nih.gov}}, biburl = {https://www.bibsonomy.org/bibtex/2daf39ed6af88c98c01b4afd27d975527/iscpif}, cited-references = {{Bau D, 2011, NAT STRUCT MOL BIOL, V18, P107, DOI 10.1038/nsmb.1936. Bender MA, 2006, BLOOD, V108, P1395, DOI 10.1182/blood-2006-04-014431. Bender MA, 1998, BLOOD, V92, P4394. Botta M, 2010, MOL SYST BIOL, V6, DOI 10.1038/msb.2010.79. Cook PR, 2009, J CELL BIOL, V186, P825, DOI 10.1083/jcb.200903083. Cui Y, 2000, P NATL ACAD SCI USA, V97, P127, DOI 10.1073/pnas.97.1.127. de Gennes P. G., 1988, SCALING CONCEPTS POL. Dekker J, 2006, NAT METHODS, V3, P17, DOI 10.1038/NMETH823. 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This study was also supported by the Sixth European Research Framework (project number 034952, GENNETEC project), PRES UniverSud Paris, CNRS and Genopole (to F.K.). Funding for open access charge: Intramural Program, National Institute of Diabetes, and Digestive and Kidney Diseases, National Institutes of Health {[}KIA 15508 to AD].}}, interhash = {d3cc1ed6d61c7f4f99665a96189af7d8}, intrahash = {daf39ed6af88c98c01b4afd27d975527}, issn = {{0305-1048}}, journal = {{NUCLEIC ACIDS RESEARCH}}, journal-iso = {{Nucleic Acids Res.}}, keywords = {imported iscpif}, keywords-plus = {{CONTROL REGION; ERYTHROID-DIFFERENTIATION; CONFORMATION CAPTURE; GENE-EXPRESSION; CHROMATIN CONFORMATION; GENOME; REVEALS; ARCHITECTURE; INSULATORS; PRINCIPLES}}, language = {{English}}, month = {{SEP}}, number = {{16}}, number-of-cited-references = {{51}}, pages = {{7718-7727}}, publisher = {{OXFORD UNIV PRESS}}, research-areas = {{Biochemistry \& Molecular Biology}}, times-cited = {{10}}, timestamp = {2015-05-15T21:54:53.000+0200}, title = {{CTCF-mediated transcriptional regulation through cell type-specific chromosome organization in the beta-globin locus}}, type = {{Article}}, unique-id = {{ISI:000308959800019}}, volume = {{40}}, web-of-science-categories = {{Biochemistry \& Molecular Biology}}, year = 2012 }