Yana V. Bernatavichute

Bio: Yana V. Bernatavichute is an academic researcher from University of California, Los Angeles. The author has contributed to research in topics: DNA methylation & Epigenomics. The author has an hindex of 13, co-authored 14 publications receiving 4209 citations.

Relationship between nucleosome positioning and DNA methylation.

Abstract: A genome-wide analysis in the plant Arabidopsis thaliana of the positioning of the nucleosomes — the nucleoprotein molecules that organize and control access to genomic DNA — combined with profiles of DNA methylation at single-base resolution, reveals 10-base periodicities in the DNA methylation status of nucleosome-bound DNA. The results suggest that nucleosome position influences DNA methylation patterning in the genome, and that DNA methyltransferases preferentially target nucleosome-bound DNA. Similar trends were observed in human nucleosomal DNA, indicating that the relationships between nucleosomes and DNA methyltransferases are conserved. Nucleosomes are composed of around 147 bases of DNA wrapped around an octamer of histone proteins. Here, a genome-wide analysis of nucleosome positioning in Arabidopsis thaliana has been combined with profiles of DNA methylation at single base resolution, revealing 10-base periodicities in the DNA methylation status of nucleosome-bound DNA. The results indicate that nucleosome positioning influences the pattern of DNA methylation throughout the genome. Nucleosomes compact and regulate access to DNA in the nucleus, and are composed of approximately 147 bases of DNA wrapped around a histone octamer1,2. Here we report a genome-wide nucleosome positioning analysis of Arabidopsis thaliana using massively parallel sequencing of mononucleosomes. By combining this data with profiles of DNA methylation at single base resolution, we identified 10-base periodicities in the DNA methylation status of nucleosome-bound DNA and found that nucleosomal DNA was more highly methylated than flanking DNA. These results indicate that nucleosome positioning influences DNA methylation patterning throughout the genome and that DNA methyltransferases preferentially target nucleosome-bound DNA. We also observed similar trends in human nucleosomal DNA, indicating that the relationships between nucleosomes and DNA methyltransferases are conserved. Finally, as has been observed in animals, nucleosomes were highly enriched on exons, and preferentially positioned at intron–exon and exon–intron boundaries. RNA polymerase II (Pol II) was also enriched on exons relative to introns, consistent with the hypothesis that nucleosome positioning regulates Pol II processivity. DNA methylation is also enriched on exons, consistent with the targeting of DNA methylation to nucleosomes, and suggesting a role for DNA methylation in exon definition.

Whole-genome analysis of histone H3 lysine 27 trimethylation in Arabidopsis.

Abstract: Trimethylation of histone H3 lysine 27 (H3K27me3) plays critical roles in regulating animal development, and in several cases, H3K27me3 is also required for the proper expression of developmentally important genes in plants. However, the extent to which H3K27me3 regulates plant genes on a genome-wide scale remains unknown. In addition, it is not clear whether the establishment and spreading of H3K27me3 occur through the same mechanisms in plants and animals. We identified regions containing H3K27me3 in the genome of the flowering plant Arabidopsis thaliana using a high-density whole-genome tiling microarray. The results suggest that H3K27me3 is a major silencing mechanism in plants that regulates an unexpectedly large number of genes in Arabidopsis (~4,400), and that the maintenance of H3K27me3 is largely independent of other epigenetic pathways, such as DNA methylation or RNA interference. Unlike in animals, where H3K27m3 occupies large genomic regions, in Arabidopsis, we found that H3K27m3 domains were largely restricted to the transcribed regions of single genes. Furthermore, unlike in animals systems, H3K27m3 domains were not preferentially associated with low-nucleosome density regions. The results suggest that different mechanisms may underlie the establishment and spreading of H3K27me3 in plants and animals.

Genome-wide analysis of mono-, di- and trimethylation of histone H3 lysine 4 in Arabidopsis thaliana

Abstract: Background: Post-translational modifications of histones play important roles in maintaining normal transcription patterns by directly or indirectly affecting the structural properties of the chromatin. In plants, methylation of histone H3 lysine 4 (H3K4me) is associated with genes and required for normal plant development. Results: We have characterized the genome-wide distribution patterns of mono-, di- and trimethylation of H3K4 (H3K4me1, H3K4me2 and H3K4me3, respectively) in Arabidopsis thaliana seedlings using chromatin immunoprecipitation and high-resolution whole-genome tiling microarrays (ChIP-chip). All three types of H3K4me are found to be almost exclusively genic, and two-thirds of Arabidopsis genes contain at least one type of H3K4me. H3K4me2 and H3K4me3 accumulate predominantly in promoters and 5' genic regions, whereas H3K4me1 is distributed within transcribed regions. In addition, H3K4me3-containing genes are highly expressed with low levels of tissue specificity, but H3K4me1 or H3K4me2 may not be directly involved in transcriptional activation. Furthermore, the preferential co-localization of H3K4me3 and H3K27me3 found in mammals does not appear to occur in plants at a genome-wide level, but H3K4me2 and H3K27me3 co-localize at a higher-than-expected frequency. Finally, we found that H3K4me2/3 and DNA methylation appear to be mutually exclusive, but surprisingly, H3K4me1 is highly correlated with CG DNA methylation in the transcribed regions of genes. Conclusions: H3K4me plays widespread roles in regulating gene expression in plants. Although many aspects of the mechanisms and functions of H3K4me appear to be conserved among all three kingdoms, we observed significant differences in the relationship between H3K4me and transcription or other epigenetic pathways in plants and mammals.

Functions of DNA methylation: islands, start sites, gene bodies and beyond

Abstract: DNA methylation is frequently described as a 'silencing' epigenetic mark, and indeed this function of 5-methylcytosine was originally proposed in the 1970s. Now, thanks to improved genome-scale mapping of methylation, we can evaluate DNA methylation in different genomic contexts: transcriptional start sites with or without CpG islands, in gene bodies, at regulatory elements and at repeat sequences. The emerging picture is that the function of DNA methylation seems to vary with context, and the relationship between DNA methylation and transcription is more nuanced than we realized at first. Improving our understanding of the functions of DNA methylation is necessary for interpreting changes in this mark that are observed in diseases such as cancer.

Establishing, maintaining and modifying DNA methylation patterns in plants and animals

Abstract: Cytosine DNA methylation is a stable epigenetic mark that is crucial for diverse biological processes, including gene and transposon silencing, imprinting and X chromosome inactivation. Recent findings in plants and animals have greatly increased our understanding of the pathways used to accurately target, maintain and modify patterns of DNA methylation and have revealed unanticipated mechanistic similarities between these organisms. Key roles have emerged for small RNAs, proteins with domains that bind methylated DNA and DNA glycosylases in these processes. Drawing on insights from both plants and animals should deepen our understanding of the regulation and biological significance of DNA methylation.

The Polycomb complex PRC2 and its mark in life

Abstract: Polycomb group proteins maintain the gene-expression pattern of different cells that is set during early development by regulating chromatin structure. In mammals, two main Polycomb group complexes exist — Polycomb repressive complex 1 (PRC1) and 2 (PRC2). PRC1 compacts chromatin and catalyses the monoubiquitylation of histone H2A. PRC2 also contributes to chromatin compaction, and catalyses the methylation of histone H3 at lysine 27. PRC2 is involved in various biological processes, including differentiation, maintaining cell identity and proliferation, and stem-cell plasticity. Recent studies of PRC2 have expanded our perspectives on its function and regulation, and uncovered a role for non-coding RNA in the recruitment of PRC2 to target genes.

Epigenetic modifications and human disease

Abstract: Epigenetics is one of the most rapidly expanding fields in biology. The recent characterization of a human DNA methylome at single nucleotide resolution, the discovery of the CpG island shores, the finding of new histone variants and modifications, and the unveiling of genome-wide nucleosome positioning maps highlight the accelerating speed of discovery over the past two years. Increasing interest in epigenetics has been accompanied by technological breakthroughs that now make it possible to undertake large-scale epigenomic studies. These allow the mapping of epigenetic marks, such as DNA methylation, histone modifications and nucleosome positioning, which are critical for regulating gene and noncoding RNA expression. In turn, we are learning how aberrant placement of these epigenetic marks and mutations in the epigenetic machinery is involved in disease. Thus, a comprehensive understanding of epigenetic mechanisms, their interactions and alterations in health and disease, has become a priority in biomedical research.