Most of the known Drosophila architectural proteins interact with an important cofactor, CP190, that contains three domains (BTB, M, and D) that are involved in protein–protein interactions. The highly conserved N-terminal CP190 BTB domain forms a stable homodimer that interacts with unstructured regions in the three best-characterized architectural proteins: dCTCF, Su(Hw), and Pita. Here, we identified two new CP190 partners, CG4730 and CG31365, that interact with the BTB domain. The CP190 BTB resembles the previously characterized human BCL6 BTB domain, which uses its hydrophobic groove to specifically associate with unstructured regions of several transcriptional repressors. Using GST pull-down and yeast two-hybrid assays, we demonstrated that mutations in the hydrophobic groove strongly affect the affinity of CP190 BTB for the architectural proteins. In the yeast two-hybrid assay, we found that architectural proteins use various mechanisms to improve the efficiency of interaction with CP190. Pita and Su(Hw) have two unstructured regions that appear to simultaneously interact with hydrophobic grooves in the BTB dimer. In dCTCF and CG31365, two adjacent regions interact simultaneously with the hydrophobic groove of the BTB and the M domain of CP190. Finally, CG4730 interacts with the BTB, M, and D domains of CP190 simultaneously. These results suggest that architectural proteins use different mechanisms to increase the efficiency of interaction with CP190.

Genetic diversity of native populations of North Eurasia is investigated using a panel of genetic markers of candidate genes for cold climate adaptation. A high level of within- and between-population

CP190 is a co-factor in many Drosophila architectural proteins, being involved in the formation of active promoters and insulators. CP190 contains the N-terminal BTB/POZ (Broad-Complex, Tramtrack and Bric a brac/POxvirus and Zinc finger) domain and adjacent conserved regions involved in protein interactions. Here, we examined the functional roles of these domains of CP190 in vivo. The best-characterized architectural proteins with insulator functions, Pita, Su(Hw), and dCTCF, interacted predominantly with the BTB domain of CP190. Due to the difficulty of mutating the BTB domain, we obtained a transgenic line expressing a chimeric CP190 with the BTB domain of the human protein Kaiso. Another group of architectural proteins, M1BP, Opbp, and ZIPIC, interacted with one or both of the highly conserved regions in the N-terminal part of CP190. Transgenic lines of D. melanogaster expressing CP190 mutants with a deletion of each of these domains were obtained. The results showed that these mutant proteins only partially compensated for the functions of CP190, weakly binding to selective chromatin sites. Further analysis confirmed the essential role of these domains in recruitment to regulatory regions associated with architectural proteins. We also found that the N-terminal of CP190 was sufficient for recruiting Z4 and Chromator proteins and successfully achieving chromatin opening. Taken together, our results and the results of previous studies showed that the N-terminal region of CP190 is a platform for simultaneous interaction with various DNA-binding architectural proteins and transcription complexes.

В представленном исследовании в популяционной выборке якутов изучена изменчивость частот аллелей однонуклеотидных полиморфизмов, ассоциированных с ИМТ и ожирением, по данным GWAS. Полученные результаты сопоставлены с данными по 20 популяциям из международного проекта «1000 геномов». Выявлены генетические маркеры, вносящие наибольший вклад в генетическую дифференциацию...

Gene duplication, a major source of new genes in evolution, often occurs via reverse transcription of mRNA, leading to the integration of a retrocopy into a new genomic locus. Here, we performed an in-depth analysis of the evolutionary history of the e(y)2 gene in Metazoa. The E(y)2 protein is a shared subunit of two highly conserved complexes involved in transcription regulation (the DUB module of the SAGA complex) and mRNA transport (TREX-2). In Deuterostomes, the e(y)2 gene has undergone multiple independent retropositions, often giving rise to functional retrogenes. In contrast, among Protostomes, duplications of e(y)2 were identified only in Drosophilinae and a member of the Lepidoptera family (Manduca sexta). In Drosophila, the retrocopy e(y)2 acquired an almost ubiquitous expression pattern and compensates for the function of the parental gene in all tissues except the testes. The parental gene, e(y)2b, evolved a testis-specific expression pattern, lost the ability to incorporate into the DUB module, but retained nuclear envelope localization and the capacity to assemble into the TREX-2 complex. Knockout of the D. melanogaster e(y)2b gene resulted in reduced male fertility. Overall, our study highlights distinct evolutionary trajectories of the e(y)2 gene in Deuterostomes and Protostomes.

Популяции человека проживают в различных условиях среды обитания, которые требуют адаптации, особенно к экстремальным средовым факторам. Действие адаптивной эволюции отражается и на генетической структуре популяций человека. В настоящем исследовании был проведен анализ вариабельности 25 однонуклеотидных полиморфизмов (SNP), связанных с адаптацией к холодному климату, в мировых популяциях. Показано влияние климатических и географических факторов на генетическое разнообразие популяций человека. Выявлен рост генетического разнообразия по изученным маркерам от Африки по мере расселения современного человека по земному шару. Вероятно, высокая частота аллелей, ассоциированных с адаптацией к климату, в некоторых популяциях человека может быть объяснена в рамках гипотезы канализации/деканализации геном-феномных отношений в ходе расселения современного человека.Human populations live in different environmental conditions that require adaptation, especially to extreme environmental factors. The action of adaptive evolution is also reflected on human populations’ genetic constitution. The study highlights the variability analysis of 25 SNPs single nucleotide polymorphisms (SNP) related to adaptation to a cold climate, as well as influence of climatic and geographical factors on the genetic diversity of human populations. The growth of the genetic diversity among the studied markers from Africa according to a modern human’s displacement around the earth identified. Probably, the variability of alleles associated with adaptation to climate in some populations could be explained in the framework of the hypothesis of canalization/decanalization of genome-phenome relationships under natural selection during modern human dispersion.