title: CTCF regulates NELF, DSIF and P-TEFb recruitment during transcription.
abstract: CTCF is a versatile transcription factor with well-established roles in chromatin organization and insulator function. Recent findings also implicate CTCF in the control of elongation by RNA polymerase (RNAP) II. Here we show that CTCF knockdown abrogates RNAP II pausing at the early elongation checkpoint of c-myc by affecting recruitment of DRB-sensitivity-inducing factor (DSIF). CTCF knockdown also causes a termination defect on the U2 snRNA genes (U2), by affecting recruitment of negative elongation factor (NELF). In addition, CTCF is required for recruitment of positive elongation factor b (P-TEFb), which phosphorylates NELF, DSIF, and Ser2 of the RNAP II CTD to activate elongation of transcription of c-myc and recognition of the snRNA gene-specific 3' box RNA processing signal. These findings implicate CTCF in a complex network of protein:protein/protein:DNA interactions and assign a key role to CTCF in controlling RNAP II transcription through the elongation checkpoint of the protein-coding c-myc and the termination site of the non-coding U2, by regulating the recruitment and/or activity of key players in these processes.
authors.affiliation: a Sir William Dunn School of Pathology; University of Oxford ; Oxford , UK.|e Current address: Immunocore Limited; Milton Park , Abingdon , Oxon , UK.
authors.forename: Clélia
authors.initials: C
authors.lastname: Laitem
authors.affiliation: a Sir William Dunn School of Pathology; University of Oxford ; Oxford , UK.
authors.forename: Justyna
authors.initials: J
authors.lastname: Zaborowska
authors.affiliation: a Sir William Dunn School of Pathology; University of Oxford ; Oxford , UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Tellier
authors.affiliation: b Graduate School of Bioscience and Biotechnology; Tokyo Institute of Technology ; Yokohama , Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Yamaguchi
authors.affiliation: b Graduate School of Bioscience and Biotechnology; Tokyo Institute of Technology ; Yokohama , Japan.
authors.forename: Qingfu
authors.initials: Q
authors.lastname: Cao
authors.affiliation: c Université de Toulouse; UPS; Laboratoire de Biologie Moléculaire Eucaryote ; Toulouse , France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Egloff
authors.affiliation: d Department of Nanoparticle Translational Research ; Tokyo Medical University ; Tokyo , Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Handa
authors.affiliation: a Sir William Dunn School of Pathology; University of Oxford ; Oxford , UK.
authors.forename: Shona
authors.initials: S
authors.lastname: Murphy
mesh_terms: D000076246:CCCTC-Binding Factor; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism*; D010766:Phosphorylation; D042925:Positive Transcriptional Elongation Factor B / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D012319:RNA Polymerase II / Q000378:metabolism; D012342:RNA, Small Nuclear / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D035602:Transcriptional Elongation Factors / Q000378:metabolism*
chemical_list: D000076246:CCCTC-Binding Factor; C000619697:CTCF protein, human; C489427:MYC protein, human; C411985:NSMF protein, human; D009687:Nuclear Proteins; D016271:Proto-Oncogene Proteins c-myc; D012342:RNA, Small Nuclear; D012097:Repressor Proteins; C112224:SUPT5H protein, human; D014157:Transcription Factors; D035602:Transcriptional Elongation Factors; C405484:U2 small nuclear RNA; D042925:Positive Transcriptional Elongation Factor B; D012319:RNA Polymerase II
keywords: CTCF; P-TEFb; RNA Polymerase II pausing; elongation checkpoint; snRNA gene; transcription