Farkas, C. | bioRxiv Science

bioRxiv2023

Poly(dA:dT) tracts differentially modulate nucleosome remodeling activity of RSC and ISW1a complexes, exerting tract orientation-dependent and -independent effects

The establishment and maintenance of nucleosome-free regions (NFRs) are prominent processes within chromatin dynamics. Transcription factors, ATP-dependent chromatin remodeling complexes (CRCs) and DNA sequences are the main factors involved. In Saccharomyces cerevisiae, CRCs such as RSC contribute to chromatin opening at NFRs, while other complexes, including ISW1a, contribute to NFR shrinking. Regarding DNA sequences, growing evidence point to poly(dA:dT) tracts as playing a direct role in the active processes involved in nucleosome positioning dynamics. Intriguingly, poly(dA:dT) tract-containing NFRs span asymmetrically relative to the location of the tract, by a currently unknown mechanism. In order to get insight into the role of poly(dA:dT) tracts in nucleosome remodeling, we performed a systematic analysis of their influence on the activity of ISW1a and RSC complexes, with focus on their effect when located on linker DNA. Our findings revealed that poly(dA:dT) tracts differentially affect the activity of these CRCs. Moreover, we found differences between the effects exerted by the two alternative tract orientations. Our results support a model for the asymmetric chromatin opening that take place around these sequences.

molecular biology↗

bioRxiv2020

Insights on early mutational events in SARS-CoV-2 virus reveal founder effects across geographical regions

Here we aim to describe early mutational events across samples from publicly available SARS-CoV-2 sequences from the sequence read archive repository. Up until March 27, 2020, we downloaded 53 illumina datasets, mostly from China, USA (Washington DC) and Australia (Victoria). Of 30 high quality datasets, 27 datasets (90%) contain at least a single founder mutation and most of the variants are missense (over 63%). Five-point mutations with clonal (founder) effect were found in USA sequencing samples. Sequencing samples from USA in GenBank present this signature with 50% allele frequencies among samples. Australian mutation signatures were more diverse than USA samples, but still, clonal events were found in those samples. Mutations in the helicase and orf1a coding regions from SARS-CoV-2 were predominant, among others, suggesting that these proteins are prone to evolve by natural selection. Finally, we firmly urge that primer sets for diagnosis be carefully designed, since rapidly occurring variants would affect the performance of the reverse transcribed quantitative PCR (RT-qPCR) based viral testing.

genomics↗