Biology subjects

Chereji, R. V.

Publications and source records attributed to Chereji, R. V..

3 recordsLinked to original sources

bioRxiv2019

DNA accessibility is not the primary determinant of chromatin-mediated gene regulation

DNA accessibility is thought to be of major importance in regulating gene expression. We test this hypothesis using a restriction enzyme as a probe of chromatin structure and as a proxy for transcription factors. We measured the digestion rate and the fraction of accessible DNA at all genomic AluI sites in budding yeast and mouse liver nuclei. Hepatocyte DNA is more accessible than yeast DNA, consistent with longer linkers between nucleosomes, and indicating that nucleosome spacing is a major determinant of accessibility. DNA accessibility varies from cell to cell, such that essentially no sites are accessible or inaccessible in every cell. AluI sites in inactive mouse promoters are accessible in some cells, implying that transcription factors could bind without activating the gene. Euchromatin and heterochromatin have very similar accessibilities, suggesting that transcription factors can penetrate heterochromatin. Thus, DNA accessibility is not likely to be the primary determinant of gene regulation.

genomics↗

bioRxiv2018

Transfer RNA Genes Affect Chromosome Structure and Function via Local Effects

The genome is packaged and organized in an ordered, non-random manner and specific chromatin segments contact nuclear substructures to mediate this organization. While transfer RNA genes (tDNAs) are essential for the generation of tRNAs, these loci are also binding sites for transcription factors and architectural proteins and are thought to play an important role in the organization of the genome. In this study, we investigate the role of tDNAs in genomic organization and chromosome function by editing a chromosome so that it lacks any tDNAs. Surprisingly our analyses of this tDNA-less chromosome show that loss of tDNAs does not grossly affect chromosome folding or chromosome tethering. However, loss of tDNAs affects local nucleosome positioning and the binding of SMC proteins at these loci. The absence of tDNAs also leads to changes in centromere clustering and a reduction in the frequency of long range HML-HMR heterochromatin clustering. We propose that the tDNAs primarily affect local chromatin structure that result in effects on long-range chromosome architecture.

molecular biology↗

bioRxiv2017

plot2DO: a tool to assess the quality and distribution of genomic data

SummaryMicrococcal nuclease digestion followed by deep sequencing (MNase-seq) is the most used method to investigate nucleosome organization on a genome-wide scale. We present plot2DO, a software package for creating 2D occupancy plots, which allows biologists to evaluate the quality of MNase-seq data and to visualize the distribution of nucleosomes near the functional regions of the genome (e.g. gene promoters, origins of replication, etc.).\n\nAvailability And ImplementationThe plot2DO open source package is freely available on GitHub at https://github.com/rchereji/plot2DO under the MIT license.\n\nContactrazvan.chereji@nih.gov\n\nSupplementary InformationSupplementary data are available at Bioinformatics online.

genomics↗