title: CTCF-dependent co-localization of canonical Smad signaling factors at architectural protein binding sites in D. melanogaster.
abstract: The transforming growth factor β (TGF-β) and bone morphogenetic protein (BMP) pathways transduce extracellular signals into tissue-specific transcriptional responses. During this process, signaling effector Smad proteins translocate into the nucleus to direct changes in transcription, but how and where they localize to DNA remain important questions. We have mapped Drosophila TGF-β signaling factors Mad, dSmad2, Medea, and Schnurri genome-wide in Kc cells and find that numerous sites for these factors overlap with the architectural protein CTCF. Depletion of CTCF by RNAi results in the disappearance of a subset of Smad sites, suggesting Smad proteins localize to CTCF binding sites in a CTCF-dependent manner. Sensitive Smad binding sites are enriched at low occupancy CTCF peaks within topological domains, rather than at the physical domain boundaries where CTCF may function as an insulator. In response to Decapentaplegic, CTCF binding is not significantly altered, whereas Mad, Medea, and Schnurri are redirected from CTCF to non-CTCF binding sites. These results suggest that CTCF participates in the recruitment of Smad proteins to a subset of genomic sites and in the redistribution of these proteins in response to BMP signaling.
authors.affiliation: a Department of Biology ; Emory University , Atlanta , GA USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Van Bortle
authors.forename: Aidan J
authors.initials: AJ
authors.lastname: Peterson
authors.forename: Naomi
authors.initials: N
authors.lastname: Takenaka
authors.forename: Michael B
authors.initials: MB
authors.lastname: O'Connor
authors.forename: Victor G
authors.initials: VG
authors.lastname: Corces
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D000076246:CCCTC-Binding Factor; D002460:Cell Line; D016384:Consensus Sequence; D029721:Drosophila Proteins / Q000502:physiology*; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism*; D044127:Epigenesis, Genetic; D021381:Protein Transport; D012097:Repressor Proteins / Q000502:physiology*; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism*; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000502:physiology
chemical_list: D000076246:CCCTC-Binding Factor; C524946:CTCF protein, Drosophila; D029721:Drosophila Proteins; D012097:Repressor Proteins; D051785:Smad Proteins; D016212:Transforming Growth Factor beta; C064196:dpp protein, Drosophila
keywords: BMP; TGF-β signaling; Transcription; chromatin; epigenetics; growth factor