Eukaryotic DNA is packaged into chromatin, and this chromatin has a well-defined organization. Chromatin is composed of nucleosome building blocks, whose positioning along the DNA dictates the accessibility of gene regulatory elements, and ultimately the expression levels of genes. Nucleosomes occur in regular repeating intervals on genes. These arrays are highly regulated through many mechanisms including: post- translational modifications, deposition and eviction that are facilitated by chaperones, and re-positioning facilitated by chromatin remodeling complexes. We propose to further our understanding of nucleosomal arrays on a genomic scale.
In aim 1, we will use our newly developed ultra-high resolution ChIP-exo assay to determine the subnucleosomal organization of histone marks along nucleosomal arrays across a genome.
In aim 2, we will map the nucleosomal and subnucleosomal organization of chromatin remodelers using ChIP-exo. Their placement at specific nucleosomes, and their orientation on the nucleosome surface should provide insight into how they function on a genomic scale.
In aim 3, we will use our recently developed genome-wide reconstitution of properly positioned nucleosomal arrays to probe biochemical mechanisms of chromatin remodeler-directed array formation. Completion of these aims is expected to provide an understanding of fundamental principles of nucleosomal array and their role in regulating gene expression.

Public Health Relevance

Human health is highly dependent upon the proper functioning of our genes (biological instructions). This project will contribute to a greater understanding of how genes function by determining how these genes are packaged on a global scale, and how that packaging is regulated.

National Institute of Health (NIH)
Research Project (R01)
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Genomics, Computational Biology and Technology Study Section (GCAT)
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Pazin, Michael J
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Pennsylvania State University
Schools of Arts and Sciences
University Park
United States
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Rhee, Ho Sung; Bataille, Alain R; Zhang, Liye et al. (2014) Subnucleosomal structures and nucleosome asymmetry across a genome. Cell 159:1377-88
Yen, Kuangyu; Vinayachandran, Vinesh; Pugh, B Franklin (2013) SWR-C and INO80 chromatin remodelers recognize nucleosome-free regions near +1 nucleosomes. Cell 154:1246-56
Lee, Jung-Shin; Garrett, Alexander S; Yen, Kuangyu et al. (2012) Codependency of H2B monoubiquitination and nucleosome reassembly on Chd1. Genes Dev 26:914-9
Chang, Gue Su; Noegel, Angelika A; Mavrich, Travis N et al. (2012) Unusual combinatorial involvement of poly-A/T tracts in organizing genes and chromatin in Dictyostelium. Genome Res 22:1098-106
Zhang, Zhenhai; Wippo, Christian J; Wal, Megha et al. (2011) A packing mechanism for nucleosome organization reconstituted across a eukaryotic genome. Science 332:977-80
Zhang, Zhenhai; Pugh, B Franklin (2011) Genomic organization of H2Av containing nucleosomes in Drosophila heterochromatin. PLoS One 6:e20511
Zhang, Zhenhai; Pugh, B Franklin (2011) High-resolution genome-wide mapping of the primary structure of chromatin. Cell 144:175-86
Zhang, Liye; Ma, Hong; Pugh, B Franklin (2011) Stable and dynamic nucleosome states during a meiotic developmental process. Genome Res 21:875-84
Ioshikhes, Ilya; Hosid, Sergey; Pugh, B Franklin (2011) Variety of genomic DNA patterns for nucleosome positioning. Genome Res 21:1863-71
Jiang, Cizhong; Pugh, B Franklin (2009) A compiled and systematic reference map of nucleosome positions across the Saccharomyces cerevisiae genome. Genome Biol 10:R109

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