دورية أكاديمية

CCCTC-binding factor (CTCF) and cohesin influence the genomic architecture of the Igh locus and antisense transcription in pro-B cells.

التفاصيل البيبلوغرافية
العنوان: CCCTC-binding factor (CTCF) and cohesin influence the genomic architecture of the Igh locus and antisense transcription in pro-B cells.
المؤلفون: Degner SC; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA., Verma-Gaur J, Wong TP, Bossen C, Iverson GM, Torkamani A, Vettermann C, Lin YC, Ju Z, Schulz D, Murre CS, Birshtein BK, Schork NJ, Schlissel MS, Riblet R, Murre C, Feeney AJ
المصدر: Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2011 Jun 07; Vol. 108 (23), pp. 9566-71. Date of Electronic Publication: 2011 May 23.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1091-6490 (Electronic) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Washington, DC : National Academy of Sciences
مواضيع طبية MeSH: Cell Cycle Proteins/*metabolism , Chromosomal Proteins, Non-Histone/*metabolism , Immunoglobulin Heavy Chains/*metabolism , Precursor Cells, B-Lymphoid/*metabolism , Repressor Proteins/*metabolism, Animals ; Binding Sites/genetics ; Blotting, Western ; CCCTC-Binding Factor ; Cell Cycle Proteins/genetics ; Cell Line ; Cells, Cultured ; Chromatin Immunoprecipitation ; Chromosomal Proteins, Non-Histone/genetics ; DNA, Antisense/genetics ; DNA-Binding Proteins ; Enhancer Elements, Genetic/genetics ; Immunoglobulin Heavy Chains/genetics ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Nuclear Proteins/genetics ; Nuclear Proteins/metabolism ; Phosphoproteins/genetics ; Phosphoproteins/metabolism ; Protein Binding ; RNA Interference ; RNA, Antisense/genetics ; Repressor Proteins/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Transcription, Genetic ; Cohesins
مستخلص: Compaction and looping of the ~2.5-Mb Igh locus during V(D)J rearrangement is essential to allow all V(H) genes to be brought in proximity with D(H)-J(H) segments to create a diverse antibody repertoire, but the proteins directly responsible for this are unknown. Because CCCTC-binding factor (CTCF) has been demonstrated to be involved in long-range chromosomal interactions, we hypothesized that CTCF may promote the contraction of the Igh locus. ChIP sequencing was performed on pro-B cells, revealing colocalization of CTCF and Rad21 binding at ~60 sites throughout the V(H) region and 2 other sites within the Igh locus. These numerous CTCF/cohesin sites potentially form the bases of the multiloop rosette structures at the Igh locus that compact during Ig heavy chain rearrangement. To test whether CTCF was involved in locus compaction, we used 3D-FISH to measure compaction in pro-B cells transduced with CTCF shRNA retroviruses. Reduction of CTCF binding resulted in a decrease in Igh locus compaction. Long-range interactions within the Igh locus were measured with the chromosomal conformation capture assay, revealing direct interactions between CTCF sites 5' of DFL16 and the 3' regulatory region, and also the intronic enhancer (Eμ), creating a D(H)-J(H)-Eμ-C(H) domain. Knockdown of CTCF also resulted in the increase of antisense transcription throughout the D(H) region and parts of the V(H) locus, suggesting a widespread regulatory role for CTCF. Together, our findings demonstrate that CTCF plays an important role in the 3D structure of the Igh locus and in the regulation of antisense germline transcription and that it contributes to the compaction of the Igh locus.
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معلومات مُعتمدة: R01 AI023548 United States AI NIAID NIH HHS; T32HL07195 United States HL NHLBI NIH HHS; R01AI82918 United States AI NIAID NIH HHS; R01 AI040227 United States AI NIAID NIH HHS; F32AI084418 United States AI NIAID NIH HHS; R01AI40227 United States AI NIAID NIH HHS; UL1 RR025774 United States RR NCRR NIH HHS; R01AI023548 United States AI NIAID NIH HHS; R01 AI013509 United States AI NIAID NIH HHS; R01 AI029672 United States AI NIAID NIH HHS; R37 AI040227 United States AI NIAID NIH HHS; R01AI082850 United States AI NIAID NIH HHS; R01 AI082918 United States AI NIAID NIH HHS; R01AI13509 United States AI NIAID NIH HHS; F32 AI084418 United States AI NIAID NIH HHS; T32 HL007195 United States HL NHLBI NIH HHS; R01 AI082850 United States AI NIAID NIH HHS; R01AI29672 United States AI NIAID NIH HHS
سلسلة جزيئية: GEO GSE26257
المشرفين على المادة: 0 (CCCTC-Binding Factor)
0 (Cell Cycle Proteins)
0 (Chromosomal Proteins, Non-Histone)
0 (Ctcf protein, mouse)
0 (DNA, Antisense)
0 (DNA-Binding Proteins)
0 (Immunoglobulin Heavy Chains)
0 (Nuclear Proteins)
0 (Phosphoproteins)
0 (RNA, Antisense)
0 (Rad21 protein, mouse)
0 (Repressor Proteins)
تواريخ الأحداث: Date Created: 20110525 Date Completed: 20110826 Latest Revision: 20231213
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC3111298
DOI: 10.1073/pnas.1019391108
PMID: 21606361
قاعدة البيانات: MEDLINE
الوصف
تدمد:1091-6490
DOI:10.1073/pnas.1019391108