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 ␤-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 and ␥ globin, which are active in the embryonic yolk sac, contain regions which are histone associated in the sperm. No histoneassociated regions are present at the sites tested within the ␤-and ␦-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.Complex rearrangements of the sperm chromatin occur during mammalian spermatogenesis. In the elongating spermatids, the histones associated with the DNA are displaced by transition proteins, which in turn are replaced by protamines. As a result of this process, the chromatin in the spermatozoa is highly condensed (17). In human sperm, approximately 15% of the DNA remains associated with histones in a sequence-specific manner (12,25). The histones in sperm chromatin are a subset of the histones found in somatic chromatin (13), and they form nucleosomes which are more closely packed than those found in somatic cells (4). Histone H1 is absent, histone H2 takes the form of two minor variants, called H2A.X and H2A.Z, and the histones H3 and H4 are extensively acetylated (13). Absence of histone H1 and acetylation of histones are both features of active chromatin (28,29). This has led to the suggestion that histones in sperm could influence which genes are first transcribed after fertilization (12).To explore the impact of sperm chromatin on temporal gene regulation, we analyzed the ␤-globin family of genes which are transcribed at different times during development. The ␤-globin locus from 5Ј to 3Ј consists of the locus control region (LCR) and the ε-, G ␥-, A ␥-, ␦-, and ␤-globin genes. Only the ε-and ␥-globin genes are transcribed in the primitive erythroblasts in the embryonic yolk sac which differentiates at 3 weeks of gestation. The expression of the ␥-globin gene predominates during the fetal period when the site of erythropoiesis shifts to the definitive erythroblasts in the fetal liver. The ␦-globin gene product i...

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The functional diversity of skeletal muscle is largely determined by the combinations of contractile protein isoforms that are expressed in different fibers. Just how the developmental expression of this large array of genes is regulated to give functional phenotypes is thus of great interest. In the present study, we perform a comprehensive analysis of contractile protein isoform mRNA profiles in skeletal muscle systems representing each generation of fiber formed: primary, secondary, and regenerating fibers. We find that in each system examined there is a common pattern of isoform gene expression during early differentiation for 5 of the 6 gene families we have investigated: myosin light chain (MLCI1, MLC2, tropomyosin, troponin (Tn)C, and TnI. We suggest that the common isoform patterns observed together represent a genetic program of skeletal muscle differentiation that is independent of the mature fiber phenotype and is found in all newly formed myotubes. Within each of these contractile protein gene families the program is independent of the isoforms of myosin heavy chain (MHC) expressed. The maintenance of such a program may reflect a specific requirement of the initial differentiation process. 0 1993 Wiley-Liss, Inc.