Boundary Associated Long Noncoding RNA Mediates Long-Range Chromosomal Interactions.

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 l...

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Main Authors: Ifeoma Jane Nwigwe, Yoon Jung Kim, David A Wacker, Tae Hoon Kim
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2015-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC4547746?pdf=render
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author Ifeoma Jane Nwigwe
Yoon Jung Kim
David A Wacker
Tae Hoon Kim
author_facet Ifeoma Jane Nwigwe
Yoon Jung Kim
David A Wacker
Tae Hoon Kim
author_sort Ifeoma Jane Nwigwe
collection DOAJ
description 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.
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spelling doaj.art-12180ac3024749bfafe1962d18bcb5172022-12-22T03:09:51ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01108e013610410.1371/journal.pone.0136104Boundary Associated Long Noncoding RNA Mediates Long-Range Chromosomal Interactions.Ifeoma Jane NwigweYoon Jung KimDavid A WackerTae Hoon KimCCCTC 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.http://europepmc.org/articles/PMC4547746?pdf=render
spellingShingle Ifeoma Jane Nwigwe
Yoon Jung Kim
David A Wacker
Tae Hoon Kim
Boundary Associated Long Noncoding RNA Mediates Long-Range Chromosomal Interactions.
PLoS ONE
title Boundary Associated Long Noncoding RNA Mediates Long-Range Chromosomal Interactions.
title_full Boundary Associated Long Noncoding RNA Mediates Long-Range Chromosomal Interactions.
title_fullStr Boundary Associated Long Noncoding RNA Mediates Long-Range Chromosomal Interactions.
title_full_unstemmed Boundary Associated Long Noncoding RNA Mediates Long-Range Chromosomal Interactions.
title_short Boundary Associated Long Noncoding RNA Mediates Long-Range Chromosomal Interactions.
title_sort boundary associated long noncoding rna mediates long range chromosomal interactions
url http://europepmc.org/articles/PMC4547746?pdf=render
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