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Biology subjects

Medvedeva, Y. A.

Publications and source records attributed to Medvedeva, Y. A..

4 recordsLinked to original sources

Functional characterization of DNAAF3-AS1 in chromatin remodeling and H3K36me3 distribution

Long non-coding RNAs (lncRNAs) represent a diversity of transcripts that can regulate gene expression and chromatin remodelling. DNAAF3-AS1 is an lncRNA with a strong genome-wide correlation between DNAAF3-AS1 expression and the histone mark H3K36me3, according to the HiMoRNA database. To validate this association, we performed DNAAF3-AS1 knockdown in human dermal fibroblasts using antisense oligonucleotides following H3K36me3 ChIP-seq. Our results demonstrate that DNAAF3-AS1 depletion leads to a significant redistribution of H3K36me3, with increased signal in intergenic regions and the first exon, and reduced enrichment across gene bodies. Additionally, differential expression analysis revealed that DNAAF3-AS1 knockdown induces promoter switching, with downregulation of gene-body promoters downstream of TSS. These findings establish DNAAF3-AS1 as a potential regulator of H3K36me3 deposition and transcriptional architecture, providing mechanistic insight into lncRNA-mediated epigenetic control.

cell biology↗

Hobotnica: exploring molecular signature quality

A Molecular Features Set (MFS), is a result of vast diversity of bioinformatics pipelines. In case when MFS is used for further analysis to distinguish between phenotypes, it is often referred to as a signature. Lack of the "gold standard" for most experimental data modalities makes it hard to provide valid estimation for a particular MFSs quality. Yet, this goal can partially be achieved by analyzing inner-sample Distance Matrix (DM) and their power to distinguish between phenotypes. The quality of a DM can be assessed by summarizing its power to quantify the differences of inner-phenotype and outer-phenotype distances. This estimation of the DM quality can be construed as a measure of the MFSs quality. Here we propose Hobotnica, an approach to estimate MFSs quality by their ability to stratify data, and assign them significance scores, that allows for collating various signatures and comparing their quality for contrasting groups.

bioinformatics↗

RADICL-seq identifies general and cell type-specific principles of genome-wide RNA-chromatin interactions

Mammalian genomes encode tens of thousands of noncoding RNAs. Most noncoding transcripts exhibit nuclear localization and several have been shown to play a role in the regulation of gene expression and chromatin remodelling. To investigate the function of such RNAs, methods to massively map the genomic interacting sites of multiple transcripts have been developed. However, they still present some limitations. Here, we introduce RNA And DNA Interacting Complexes Ligated and sequenced (RADICL-seq), a technology that maps genome-wide RNA-chromatin interactions in intact nuclei. RADICL-seq is a proximity ligation-based methodology that reduces the bias for nascent transcription, while increasing genomic coverage and unique mapping rate efficiency compared to existing methods. RADICL-seq identifies distinct patterns of genome occupancy for different classes of transcripts as well as cell type-specific RNA-chromatin interactions, and emphasizes the role of transcription in the establishment of chromatin structure.

genomics↗

CpG traffic lights are markers of regulatory regions in humans

DNA methylation is involved in regulation of gene expression. Although modern methods profile DNA methylation at single CpG sites, methylation levels are usually averaged over genomic regions in the downstream analyses. In this study we demonstrate that single CpG methylation can serve as a more accurate predictor of gene expression compared to average promoter / gene body methylation. CpG positions with significant correlation between methylation and expression of a gene nearby (named CpG traffic lights) are evolutionary conserved and enriched for exact TSS positions and active enhancers. Among all promoter types, CpG traffic lights are especially enriched in poised promoters. Genes that harbor CpG traffic lights are associated with development and signal transduction. Methylation levels of individual CpG traffic lights vary between cell types dramatically with the increased frequency of intermediate methylation levels, indicating cell population heterogeneity in CpG methylation levels. Being in line with the concept of the inherited stochastic epigenetic variation, methylation of such CpG positions might contribute to transcriptional regulation. Alternatively, one can hypothesize that traffic lights are markers of absent gene expression resulting from inactivation of their regulatory elements. The CpG traffic lights provide a promising insight into mechanisms of enhancer activity and gene regulation linking methylation of single CpG to expression.

bioinformatics↗