Gene expression is regulated by many factors, including transcription factors, chromatin three-dimensional topology, modifications of DNA and histone proteins, and non-coding RNAs. The execution of these complex mechanisms requires an effectively coordinated regulation system. In this review, we emphasize that the multi-scale heterogeneous DNA sequence plays a fundamental and important role for gene expression activity and usage of different means of epigenetic regulation. We illustrate here that the chromatin structure organization provides a stage for spatiotemporal regulation between different genes or gene modules and to realize their downstream functional cooperation. Such a perspective expands our understanding of the central dogma: In addition to one-dimensional sequence information, inter-gene interactions can also be transferred from DNA and RNA to protein levels.