The human genome encodes for hundreds of transcriptional programs, which facilitates the unique functions and morphologies presented by different cell types. Only recently, the role of DNA packaging into chromatin emerged as one of the major contributors to the modularity and dynamics of the genome. Here, I propose to harness my computational expertise with vast amounts of publicly available data in mice and humans, and study the internal modularity and dynamics of genome packaging, and its relation to the expression levels of underlying genes in various conditions.Specifically, the objectives of this proposal are fourfold: (1) Identify chromatin domains at a genome-wide scale. I will analyze data from hundreds of genome-wide chromatin tracks, and develop computational algorithms to segment the genome into atomic units of chromatin packaging, that open and close as homogenous blocks under various conditions and transcriptional programs. (2) Annotate and understand the functional roles of each domain. I will utilize public gene expression data and genomic maps of chromatin modifiers to annotate the role of each chromatin block, and construct an unbiased comprehensive map of the genome packaging. (3) Study the mechanisms that define, maintain and modify chromatin domains. Using sequence motifs and published binding data, I will identify chromatin regulators involved in differential domains. (4) The role of aberrant chromatin packaging in cancerous tissues. I will contrast the above domains with chromatin in cancerous tissues, and link differences to transcriptional abnormalities, thus producing a detailed set of testable hypotheses regarding the mechanisms and progression of tumors.With proven experience and proven background in genomics and computation and algorithms, I am poised to significantly contribute to our understanding of genome packaging and transcriptional regulation.