With advances in DNA sequencing and human genome project, almost all the ~20,000 genes are identified. Since less than 2% genomic DNA is coding for genes, the function of the vast majority of the genome is largely unknown and non-coding regions are used to be considered as "junk DNAs". Recent national ENCODE and Roadmap Epigenomics projects have revealed the structural and regulatory nature of these regions: there are hidden protein-chromatin and long range 3D chromatin-interaction structures, and such chromatin interaction and epigenetic regulation play important roles during development and differentiation. Identifying these regulatory regions and the higher order topological interacting structures is the key to answer the question: how different types of cells are made and controlled by the same identical DNA genome within a human individual? I will introduce new computational advances (using Bayesian Change Point segmentation and Logistic regression, etc.) in dissecting next-generation sequencing (NGS) data generated by ChIP-seq and Hi-C/ChIA-PET, that are the most powerful genome-wide chromatin structure mapping tools.