Human spermatogenesis as a model to examine gene potentiation.

The first tier of control over the expression of genic domains utilizes chromatin structure. Before the onset of transcription, the chromatin domain that encompasses the gene(s) must assume an open conformation. This renders large segments of the genome available to the tissue-specific and ubiquitous trans-factors necessary for proper expression of the genes present. This process has been termed potentiation. It is a necessary obligate, but alone it is not sufficient for gene expression. Spermatogenesis, the development of a viable fertile male gamete, provides a unique model to begin to address the underlying mechanism(s) governing differentiation and tissue-specific gene expression. Male gametogenesis is typified by the activation of numerous genes whose products have novel functions, as well as testis-specific forms of constitutively expressed somatic genes. We have shown that mouse spermatogenesis represents a selective potentiative process (Kramer et al., 1998: Development 125:4749-4655), but little is known about its human counterpart. To fill this void we have examined the potentiative state of several spermatid-expressed genes during the latter stages of human spermatogenesis. We have shown that spermatidexpressed genes are potentiated by the pachytene stage of differentiation. Furthermore, we establish that a chromatin domain functions as a discrete structural unit during differentiation. Interestingly, some of these open structures are maintained in the mature spermatozoon.