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TBP-Related Factor 2 as a Trigger for Robertsonian Translocations and Speciation

Robertsonian (centric-fusion) translocation is the form of chromosomal translocation in which two long arms of acrocentric chromosomes are fused to form one metacentric. These translocations reduce the number of chromosomes while preserving existing genes and are considered to contribute to speciati...

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Autores principales: Cherezov, Roman O., Vorontsova, Julia E., Simonova, Olga B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700478/
https://www.ncbi.nlm.nih.gov/pubmed/33238614
http://dx.doi.org/10.3390/ijms21228871
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author Cherezov, Roman O.
Vorontsova, Julia E.
Simonova, Olga B.
author_facet Cherezov, Roman O.
Vorontsova, Julia E.
Simonova, Olga B.
author_sort Cherezov, Roman O.
collection PubMed
description Robertsonian (centric-fusion) translocation is the form of chromosomal translocation in which two long arms of acrocentric chromosomes are fused to form one metacentric. These translocations reduce the number of chromosomes while preserving existing genes and are considered to contribute to speciation. We asked whether hypomorphic mutations in genes that disrupt the formation of pericentromeric regions could lead to centric fusion. TBP-related factor 2 (Trf2) encodes an alternative general transcription factor. A decrease of TRF2 expression disrupts the structure of the pericentromeric regions and prevents their association into chromocenter. We revealed several centric fusions in two lines of Drosophila melanogaster with weak Trf2 alleles in genetic experiments. We performed an RNAi-mediated knock-down of Trf2 in Drosophila and S2 cells and demonstrated that Trf2 upregulates expression of D1—one of the major genes responsible for chromocenter formation and nuclear integrity in Drosophila. Our data, for the first time, indicate that Trf2 may be involved in transcription program responsible for structuring of pericentromeric regions and may contribute to new karyotypes formation in particular by promoting centric fusion. Insight into the molecular mechanisms of Trf2 function and its new targets in different tissues will contribute to our understanding of its phenomenon.
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spelling pubmed-77004782020-11-30 TBP-Related Factor 2 as a Trigger for Robertsonian Translocations and Speciation Cherezov, Roman O. Vorontsova, Julia E. Simonova, Olga B. Int J Mol Sci Article Robertsonian (centric-fusion) translocation is the form of chromosomal translocation in which two long arms of acrocentric chromosomes are fused to form one metacentric. These translocations reduce the number of chromosomes while preserving existing genes and are considered to contribute to speciation. We asked whether hypomorphic mutations in genes that disrupt the formation of pericentromeric regions could lead to centric fusion. TBP-related factor 2 (Trf2) encodes an alternative general transcription factor. A decrease of TRF2 expression disrupts the structure of the pericentromeric regions and prevents their association into chromocenter. We revealed several centric fusions in two lines of Drosophila melanogaster with weak Trf2 alleles in genetic experiments. We performed an RNAi-mediated knock-down of Trf2 in Drosophila and S2 cells and demonstrated that Trf2 upregulates expression of D1—one of the major genes responsible for chromocenter formation and nuclear integrity in Drosophila. Our data, for the first time, indicate that Trf2 may be involved in transcription program responsible for structuring of pericentromeric regions and may contribute to new karyotypes formation in particular by promoting centric fusion. Insight into the molecular mechanisms of Trf2 function and its new targets in different tissues will contribute to our understanding of its phenomenon. MDPI 2020-11-23 /pmc/articles/PMC7700478/ /pubmed/33238614 http://dx.doi.org/10.3390/ijms21228871 Text en © 2020 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
Cherezov, Roman O.
Vorontsova, Julia E.
Simonova, Olga B.
TBP-Related Factor 2 as a Trigger for Robertsonian Translocations and Speciation
title TBP-Related Factor 2 as a Trigger for Robertsonian Translocations and Speciation
title_full TBP-Related Factor 2 as a Trigger for Robertsonian Translocations and Speciation
title_fullStr TBP-Related Factor 2 as a Trigger for Robertsonian Translocations and Speciation
title_full_unstemmed TBP-Related Factor 2 as a Trigger for Robertsonian Translocations and Speciation
title_short TBP-Related Factor 2 as a Trigger for Robertsonian Translocations and Speciation
title_sort tbp-related factor 2 as a trigger for robertsonian translocations and speciation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700478/
https://www.ncbi.nlm.nih.gov/pubmed/33238614
http://dx.doi.org/10.3390/ijms21228871
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