Retroposon DNA in sperm nucleosomal chromatin

Spermatozoa are traditionally regarded as metabolically inactive cells, whose exclusive function lies in the contribution of the paternal genome to the diploid zygote. This view rests upon the observation that these cells have essentially developed a large head, containing the male genome in a tightly packed structure, and a flagellum that acts as the motorial apparatus; the cytoplasmic portion of sperm cells is extremely reduced and lacks most, if not all, metabolic functions characteristic of somatic cells. In the last few years, we have devoted much effort to clarify the molecular mechanism of the interaction of sperm cells with exogenous DNA molecules underlying sperm-mediated gene transfer (reviewed by Spadafora, 1998). While studying this process, we have observed unexpected features of spermatozoa that have deeply modified our view that these cells are metabolically inert. Briefly, we have found that the binding of exogenous DNA molecules to sperm cells is mediated by a specific class of DNA-binding proteins (Zani et al., 1995), and is modulated by a conserved glycoprotein abundant in the seminal fluid of mammals or associated to spermatozoa of lower organisms (Lavitrano et al., 1992; Zani et al., 1995). A portion of sperm-bound DNA is internalized within sperm nuclei (Francolini et al., 1993) in a process mediated by CD4 molecules (Lavitrano et al., 1997). The internalized foreign DNA reaches the nuclear scaffold, in close contact with the chromosomal DNA, becomes heavily rearranged and eventually undergoes recombination events that cause the integration of exogenous sequences in the sperm genome (Zoraqi and Spadafora, 1997). Consistent with those observations is the finding that the interaction of exogenous DNA with sperm cells activates endogenous nucleases in a DNA dose-dependent manner (Maione et al., 1997). Sperm nucleases heavily degrade the foreign DNA and can also locally degrade sperm chromosomal DNA, suggesting that discrete sites of hypersensitivity exist within the tightly packed chromatin of mature sperm cells. Thus, otherwise silent enzymatic activities 3537 Journal of Cell Science 112, 3537-3548 (1999) Printed in Great Britain © The Company of Biologists Limited 1999 JCS0584