Jabbari, Kamel, Heger, Peter ORCID: 0000-0003-2583-2981, Sharma, Ranu and Wiehe, Thomas ORCID: 0000-0002-8932-2772 (2018). The Diverging Routes of BORIS and CTCF: An Interactomic and Phylogenomic Analysis. Life-Basel, 8 (1). BASEL: MDPI. ISSN 2075-1729

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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.

Item Type: Journal Article
CreatorsEmailORCIDORCID Put Code
Heger, PeterUNSPECIFIEDorcid.org/0000-0003-2583-2981UNSPECIFIED
Wiehe, ThomasUNSPECIFIEDorcid.org/0000-0002-8932-2772UNSPECIFIED
URN: urn:nbn:de:hbz:38-195205
DOI: 10.3390/life8010004
Journal or Publication Title: Life-Basel
Volume: 8
Number: 1
Date: 2018
Publisher: MDPI
Place of Publication: BASEL
ISSN: 2075-1729
Language: English
Faculty: Faculty of Mathematics and Natural Sciences
Divisions: Faculty of Mathematics and Natural Sciences > Department of Biology > Institute for Genetics
Subjects: no entry
Uncontrolled Keywords:
Biology; MicrobiologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/19520


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