Histone- and Protamine-DNA Association: Conservation of Different Patterns within the β-Globin Domain in Human Sperm

ABSTRACT

Most DNA in human sperm is bound to highly basic proteins called protamines, but a small proportion is complexed with histones similar to those found in active chromatin. This raises the intriguing possibility that histones in sperm are marking sets of genes that will be preferentially activated during early development. We have examined the chromatin structure of members of the β-globin gene family, which are expressed at different times in development, and the protamine 2 gene, which is expressed in spermatids prior to the widespread displacement of histones by transition proteins. The genes coding for ɛ and γ globin, which are active in the embryonic yolk sac, contain regions which are histone associated in the sperm. No histone-associated regions are present at the sites tested within the β- and δ-globin genes which are silent in the embryonic yolk sac. The trends of histone or protamine association are consistent for samples from the same person, and no significant between-subject variations in these trends are found for 13 of the 15 fragments analyzed in the two donors. The results suggest that sperm chromatin structures are generally similar in different men but that the length of the histone-associated regions can vary. The association of sperm DNA with histones or protamines sometimes changes within as little as 400 bp of DNA, suggesting that there is fine control over the retention of histones.

ACKNOWLEDGMENTS

We are grateful to David Tremethick for helpful discussions and to Peter Rowe, Merlin Crossley, David Tremethick, and Emma Whitelaw for comments on the manuscript.

This work was supported by project grant 940497 from the National Health and Medical Research Council of Australia.