title: Boundary Associated Long Noncoding RNA Mediates Long-Range Chromosomal Interactions.
abstract: CCCTC binding factor (CTCF) is involved in organizing chromosomes into mega base-sized, topologically associated domains (TADs) along with other factors that define sub-TAD organization. CTCF-Cohesin interactions have been shown to be critical for transcription insulation activity as it stabilizes long-range interactions to promote proper gene expression. Previous studies suggest that heterochromatin boundary activity of CTCF may be independent of Cohesin, and there may be additional mechanisms for defining topological domains. Here, we show that a boundary site we previously identified known as CTCF binding site 5 (CBS5) from the homeotic gene cluster A (HOXA) locus exhibits robust promoter activity. This promoter activity from the CBS5 boundary element generates a long noncoding RNA that we designate as boundary associated long noncoding RNA-1 (blncRNA1). Functional characterization of this RNA suggests that the transcript stabilizes long-range interactions at the HOXA locus and promotes proper expression of HOXA genes. Additionally, our functional analysis also shows that this RNA is not needed in the stabilization of CTCF-Cohesin interactions however CTCF-Cohesin interactions are critical in the transcription of blncRNA1. Thus, the CTCF-associated boundary element, CBS5, employs both Cohesin and noncoding RNA to establish and maintain topologically associated domains at the HOXA locus.
authors: Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT, 06520, United States of America.
authors: Ifeoma Jane
authors: IJ
authors: Nwigwe
authors: Center for Systems Biology and Department of Biological Sciences, The University of Texas at Dallas, Richardson, TX, 75080, United States of America.
authors: Yoon Jung
authors: YJ
authors: Kim
authors: Departments of Internal and Emergency Medicine, University of Maryland School of Medicine, Baltimore, MD, 21201, United States of America.
authors: David A
authors: DA
authors: Wacker
authors: Center for Systems Biology and Department of Biological Sciences, The University of Texas at Dallas, Richardson, TX, 75080, United States of America.
authors: Tae Hoon
authors: TH
authors: Kim
mesh_terms: D001665:Binding Sites; D000076246:CCCTC-Binding Factor; D018797:Cell Cycle Proteins / Q000235:genetics; D002843:Chromatin / Q000235:genetics; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics; D005347:Fibroblasts; D005786:Gene Expression Regulation; D006570:Heterochromatin / Q000235:genetics; D018398:Homeodomain Proteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D011401:Promoter Regions, Genetic; D011485:Protein Binding / Q000235:genetics; D062085:RNA, Long Noncoding / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D014158:Transcription, Genetic; D000097722:Cohesins
chemical_list: D000076246:CCCTC-Binding Factor; D018797:Cell Cycle Proteins; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D006570:Heterochromatin; D018398:Homeodomain Proteins; D062085:RNA, Long Noncoding; D012097:Repressor Proteins; D000097722:Cohesins; C000619697:CTCF protein, human; C000607592:boundary associated long noncoding RNA-1, human; C088144:HoxA protein