Although the genome is defined by its primary sequence, its functional properties, are determined by far more complex mechanisms and depend on multiple layers of nuclear organization. The architecture of the nucleus includes two overlapping structures: the chromatin and a framework structure named the nuclear matrix. Ultra-structural studies reveal that the nuclear matrix is a network consisting of branched core filaments masked with a large number of hnRNPs and regulatory proteins. This scaffold has been demonstrated to be an active and dynamic structure, anchoring the nuclear processes such as replication, transcription and splicing making nuclear domains/foci. It is postulated that the nuclear matrix serves as a dynamic support to bring together specific DNA sequences with factors involved in the regulation of genome functions. In this review, we attempt to introduce the structure and function of nuclear matrix as an active intra-nuclear factor, having a critical dynamic role to organize different nuclear functions. Studying in vivo variations of this epigenetic parameter has been suggested to all investigators interested in the field of chromatin structure and itsdynamics.