DNA loop domain organization: the three-dimensional genomic code

It is well known that aberrations in the nuclear matrix contribute to the development of cancer, but many aspects of this process remain unknown. The mammalian sperm nuclear matrix serves as a distinctive model of DNA loop domain organization by the nuclear matrix since the integrity of the DNA structure can be measured by the ability of the paternal chromosomes to participate in embryogenesis. The structure of the nuclear matrix is known to be important for normal cellular functions such as transcriptional regulation and DNA replication. Even small aberrations in DNA structural organization in the sperm cell could have disastrous consequences for the embryo if they were essential for function. Recent work from our laboratory suggests that sperm nuclei with disrupted nuclear matrix structures but intact DNA cannot participate fully in embryogenesis, suggesting that the structural organization of DNA may provide important, heritable information that is necessary for development. We term the DNA sequence together with its three-dimensional organization the "genomic code." We suggest that the sperm nucleus is an ideal model for understanding the principles of the involvement of the three-dimensional structure of DNA in normal cellular function. Finally, the implications for cancer about what we can learn using sperm DNA as a model about the "genomic code" are discussed. J. Cell. Biochem. Suppl. 35:23-26, 2000.