Characterization of nucleosome-depleted regions of transcriptionally active chromatin in chicken and human genomes

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Date
2020-08-29
Authors
Beacon, Tasnim H.
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Abstract
The mammalian genome is organized into spatial domains at multiple scales such as compartments, topologically associating domains and chromatin loops. Such folding of the genome is essential to modulate gene expression at the structural and functional level. Histone post-translational modifications (acetylated histones, H3K4me3 and H3K27ac) associated with transcriptionally active chromatin regions are referred to as active histone marks and are often associated with the active compartment (compartment A). Current evidence suggests that protein arginine-N-methyl transferases and their catalyzed histone post-translational modifications, H3R2me2s and H4R3me2a, are also associated with compartment A and are involved in establishing and maintaining the transcriptionally active chromatin state in vertebrate genomes. DNase I sensitivity and dynamic histone acetylation are features of transcribed chromatin. Within the DNase I sensitive region are DNase I hypersensitive sites which are devoid of nucleosomes and mark the presence of regulatory elements (e.g. promoters and enhancers) in the genome. Nucleosomes in the regulatory regions are destabilized by histone post-translational modifications and chromatin remodelling enzymes. Therefore, to understand the organization of transcriptionally active chromatin architecture, it is crucial to characterize the nucleosome-depleted regions of the genome in relation to nucleosome dynamics. For my project, I am investigating the features of nucleosome depleted regions in the chicken and human genomes. I have applied the technique of formaldehyde-assisted isolation of regulatory elements (FAIRE) coupled with next-generation sequencing to map out the position of the regulatory regions in relation to the active marks. FAIRE-sequencing was compared to chromatin immunoprecipitation-sequencing of H3K4me3, H3K27ac, H3R2me2s and H4R3me2a. Based on the sequenced data, FAIRE-sequencing readily identified all of the promoter regions in chicken polychromatic erythrocytes. Further I identified regions that had an atypical chromatin structure in avian and human cells, and in these regions were genes involved in cell identity. Chromatin signatures characterized in active genes, which were involved in different biological processes, were comparable to the chromatin features observed in human genome.
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Open chromatin, Nucleosome, Faire-seq, ChIP-seq, Bioinformatics
Citation
Jahan, S., Beacon, T. H., Xu, W., and Davie, J. R. (2020) Atypical chromatin structure of immune-related genes expressed in chicken erythrocytes. Biochemistry and Cell Biology 98, 171–177.
Beacon, T. H., Xu, W., and Davie, J. R. (2020) Genomic landscape of transcriptionally active histone arginine methylation marks, H3R2me2s and H4R3me2a, relative to nucleosome depleted regions. Gene 742.
Jahan, S., Beacon, T. H., He, S., Gonzalez, C., Xu, W., et al. (2019) Chromatin organization of transcribed genes in chicken polychromatic erythrocytes. Gene 699, 80–87.
Sepehri, Z., Beacon, T.H., Osman, F.D.S., Jahan, S. and Davie, J.R. (2019). DNA Methylation and Chromatin Modifications. 1st ed. Elsevier Inc., Chapter-2. Nutritional Epigenomics.