The impact factors of 3D genome organization

The 3D architecture of chromosomes is involved in the precision regulation of gene expression, and the changes in spatial conformation of chromosomes, accordingly, influence the biological processes in a cell. Recent findings in 3D genomics, through technological advances in approaches combining chromosome conformation capture (3C) and DNA sequencing, have greatly improved our understanding that how the chromatin is folded. The chromosomes are tightly packed in the nucleus with hierarchical structural units, and these units are influenced by many factors such as DNA sequence itself and the associated protein complex. In this review, we focus on the major impact factors of 3D genome organization, including the primary DNA sequences and the covalent modification of DNA (e.g. methylation); the protein complexes interplaying with gene structures and cis regulatory elements; nucleosome positioning and histone modifications; and how the structure of 3D genome changes in mitosis and polyploidization. We highlight the importance of 3D genome research by summarizing the current situation and progresses in studies of the impact factors of chromatin structure. We also discuss the critical challenges in the field, and propose the future directions as well as the potential applications in diseases.