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

• Main Authors: Roman O. Cherezov, Julia E. Vorontsova, Olga B. Simonova
• Format: Article
• Language: English
• Published: MDPI AG 2020-11-01
• Series: International Journal of Molecular Sciences
• Subjects: centric fusion; nondisjunction; pericentromeric regions; chromocenter; TATA-box-binding protein-related factor; D1 chromosomal protein
• Online Access: https://www.mdpi.com/1422-0067/21/22/8871

Robertsonian (сentric-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. <i>TBP-related factor</i> 2 (<i>Trf2</i>) 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 <i>Drosophila</i><i>melanogaster</i> with weak <i>Trf2</i> alleles in genetic experiments. We performed an RNAi-mediated knock-down of <i>Trf2</i> in <i>Drosophila</i> and <i>S2</i> cells and demonstrated that Trf2 upregulates expression of <i>D1</i>—one of the major genes responsible for chromocenter formation and nuclear integrity in <i>Drosophila</i>. 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.