The linear form of DNA sequences in a human genome is about 2 meters long,which has to be folded in micrometer-sized nuclear space for proper functions.Although most of our current understandings of the human genome functions are based on linear explanations,it has been speculated that the 3-Dimension(3D)conformation and high-order organization of the genome must play important roles in shaping the mechanisms of nuclear process such as transcription regulation and DNA replication.Recent advance in DNA sequencing has allowed the development of highthroughput technologies for mapping genome-wide chromatin interactions,and sophisticated computational programs are able to reconstitute the 3D structure of the genome.This talk will highlight the most recent advances in studying genome organization and discuss novel insights of gene transcription regulation in human diseases.