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The Diverging Routes of BORIS and CTCF: An Interactomic and Phylogenomic Analysis

The CCCTC-binding factor (CTCF) is multi-functional, ubiquitously expressed, and highly conserved from Drosophila to human. It has important roles in transcriptional insulation and the formation of a high-dimensional chromatin structure. CTCF has a paralog called “Brother of Regulator of Imprinted S...

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Autores principales: Jabbari, Kamel, Heger, Peter, Sharma, Ranu, Wiehe, Thomas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5871936/
https://www.ncbi.nlm.nih.gov/pubmed/29385718
http://dx.doi.org/10.3390/life8010004
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author Jabbari, Kamel
Heger, Peter
Sharma, Ranu
Wiehe, Thomas
author_facet Jabbari, Kamel
Heger, Peter
Sharma, Ranu
Wiehe, Thomas
author_sort Jabbari, Kamel
collection PubMed
description The CCCTC-binding factor (CTCF) is multi-functional, ubiquitously expressed, and highly conserved from Drosophila to human. It has important roles in transcriptional insulation and the formation of a high-dimensional chromatin structure. CTCF has a paralog called “Brother of Regulator of Imprinted Sites” (BORIS) or “CTCF-like” (CTCFL). It binds DNA at sites similar to those of CTCF. However, the expression profiles of the two proteins are quite different. We investigated the evolutionary trajectories of the two proteins after the duplication event using a phylogenomic and interactomic approach. We find that CTCF has 52 direct interaction partners while CTCFL only has 19. Almost all interactors already existed before the emergence of CTCF and CTCFL. The unique secondary loss of CTCF from several nematodes is paralleled by a loss of two of its interactors, the polycomb repressive complex subunit SuZ12 and the multifunctional transcription factor TYY1. In contrast to earlier studies reporting the absence of BORIS from birds, we present evidence for a multigene synteny block containing CTCFL that is conserved in mammals, reptiles, and several species of birds, indicating that not the entire lineage of birds experienced a loss of CTCFL. Within this synteny block, BORIS and its genomic neighbors seem to be partitioned into two nested chromatin loops. The high expression of SPO11, RAE1, RBM38, and PMEPA1 in male tissues suggests a possible link between CTCFL, meiotic recombination, and fertility-associated phenotypes. Using the 65,700 exomes and the 1000 genomes data, we observed a higher number of intergenic, non-synonymous, and loss-of-function mutations in CTCFL than in CTCF, suggesting a reduced strength of purifying selection, perhaps due to less functional constraint.
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spelling pubmed-58719362018-03-30 The Diverging Routes of BORIS and CTCF: An Interactomic and Phylogenomic Analysis Jabbari, Kamel Heger, Peter Sharma, Ranu Wiehe, Thomas Life (Basel) Article The CCCTC-binding factor (CTCF) is multi-functional, ubiquitously expressed, and highly conserved from Drosophila to human. It has important roles in transcriptional insulation and the formation of a high-dimensional chromatin structure. CTCF has a paralog called “Brother of Regulator of Imprinted Sites” (BORIS) or “CTCF-like” (CTCFL). It binds DNA at sites similar to those of CTCF. However, the expression profiles of the two proteins are quite different. We investigated the evolutionary trajectories of the two proteins after the duplication event using a phylogenomic and interactomic approach. We find that CTCF has 52 direct interaction partners while CTCFL only has 19. Almost all interactors already existed before the emergence of CTCF and CTCFL. The unique secondary loss of CTCF from several nematodes is paralleled by a loss of two of its interactors, the polycomb repressive complex subunit SuZ12 and the multifunctional transcription factor TYY1. In contrast to earlier studies reporting the absence of BORIS from birds, we present evidence for a multigene synteny block containing CTCFL that is conserved in mammals, reptiles, and several species of birds, indicating that not the entire lineage of birds experienced a loss of CTCFL. Within this synteny block, BORIS and its genomic neighbors seem to be partitioned into two nested chromatin loops. The high expression of SPO11, RAE1, RBM38, and PMEPA1 in male tissues suggests a possible link between CTCFL, meiotic recombination, and fertility-associated phenotypes. Using the 65,700 exomes and the 1000 genomes data, we observed a higher number of intergenic, non-synonymous, and loss-of-function mutations in CTCFL than in CTCF, suggesting a reduced strength of purifying selection, perhaps due to less functional constraint. MDPI 2018-01-30 /pmc/articles/PMC5871936/ /pubmed/29385718 http://dx.doi.org/10.3390/life8010004 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Jabbari, Kamel
Heger, Peter
Sharma, Ranu
Wiehe, Thomas
The Diverging Routes of BORIS and CTCF: An Interactomic and Phylogenomic Analysis
title The Diverging Routes of BORIS and CTCF: An Interactomic and Phylogenomic Analysis
title_full The Diverging Routes of BORIS and CTCF: An Interactomic and Phylogenomic Analysis
title_fullStr The Diverging Routes of BORIS and CTCF: An Interactomic and Phylogenomic Analysis
title_full_unstemmed The Diverging Routes of BORIS and CTCF: An Interactomic and Phylogenomic Analysis
title_short The Diverging Routes of BORIS and CTCF: An Interactomic and Phylogenomic Analysis
title_sort diverging routes of boris and ctcf: an interactomic and phylogenomic analysis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5871936/
https://www.ncbi.nlm.nih.gov/pubmed/29385718
http://dx.doi.org/10.3390/life8010004
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