25
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      The protamine family of sperm nuclear proteins

      research-article
      1 ,
      Genome Biology
      BioMed Central

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          An overview of the vertebrate members of a diverse family of basic DNA-binding proteins that are synthesized in the late-stage spermatids of many animals and plants and condense the spermatid genome into a genetically inactive state.

          Abstract

          The protamines are a diverse family of small arginine-rich proteins that are synthesized in the late-stage spermatids of many animals and plants and bind to DNA, condensing the spermatid genome into a genetically inactive state. Vertebrates have from one to 15 protamine genes per haploid genome, which are clustered together on the same chromosome. Comparison of protamine gene and amino-acid sequences suggests that the family evolved from specialized histones through protamine-like proteins to the true protamines. Structural elements present in all true protamines are a series of arginine-rich DNA-anchoring domains (often containing a mixture of arginine and lysine residues in non-mammalian protamines) and multiple phosphorylation sites. The two protamines found in mammals, P1 and P2, are the most widely studied. P1 packages sperm DNA in all mammals, whereas protamine P2 is present only in the sperm of primates, many rodents and a subset of other placental mammals. P2, but not P1, is synthesized as a precursor that undergoes proteolytic processing after binding to DNA and also binds a zinc atom, the function of which is not known. P1 and P2 are phosphorylated soon after their synthesis, but after binding to DNA most of the phosphate groups are removed and cysteine residues are oxidized, forming disulfide bridges that link the protamines together. Both P1 and P2 have been shown to be required for normal sperm function in primates and many rodents.

          Related collections

          Most cited references82

          • Record: found
          • Abstract: found
          • Article: not found

          Protamine 2 deficiency leads to sperm DNA damage and embryo death in mice.

          Cytokinesis is incomplete in spermatogenic cells, and the descendants of each stem cell form a clonal syncytium. As a result, a heterozygous mutation in a gene expressed postmeiotically affects all of the haploid spermatids within a syncytium. Previously, we have found that disruption of one copy of the gene for either protamine 1 (PRM1) or protamine 2 (PRM2) in the mouse results in a reduction in the amount of the respective protein, abnormal processing of PRM2, and inability of male chimeras to transmit either the mutant or wild-type allele derived from the 129-genotype embryonic stem cells to the next generation. Although it is believed that protamines are essential for compaction of the sperm nucleus and to protect the DNA from damage, this has not been proven experimentally. To test the hypothesis that failure of chimeras to transmit the 129 genotype to offspring was due to alterations in the organization and integrity of sperm DNA, we used the single-cell DNA electrophoresis (comet) assay, ultrastructural analysis, and the intracytoplasmic sperm injection (ICSI) procedure. Comet assay demonstrated a direct correlation between the fraction of sperm with haploinsufficiency of PRM2 and the frequency of sperm with damaged DNA. Ultrastructural analysis revealed reduced compaction of the chromatin. ICSI with PRM2-deficient sperm resulted in activation of most metaphase II-arrested mouse eggs, but few were able to develop to the blastocyst stage. These findings suggest that development fails because of damage to paternal DNA and that PRM2 is crucial for maintaining the integrity of sperm chromatin.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            The structural organization of sperm chromatin.

            The packaging of the male haploid genome within the differentiating spermatid nucleus is facilitated by small basic nuclear proteins called protamines. Although the majority of the DNA in human sperm chromatin is bound by these proteins, a small percentage retains a nucleosomal-like component. These histone-enriched regions may possess enhanced nuclease sensitivity and have been postulated to designate certain genes involved in early embryogenesis. We have shown previously that the chromatin domain containing the two human protamines PRM1 and PRM2 and the transition protein TNP2 forms a DNase I-sensitive conformation in pachytene spermatocytes, a requisite event prior to the haploid expression of its members in round spermatids (Kramer, J. A, McCarrey, J., Djakiew, D., and Krawetz, S. A. (1998) Development 125, 4749-4755). Interestingly, this configuration persists in mature spermatozoa subsequent to the transcriptional silencing of the locus. It was therefore postulated that the retained, enhanced DNase I-sensitive conformation of the PRM1-->PRM2-->TNP2 domain in human sperm may be preferentially histone-enriched. To address this tenet, we examined the chromatin structure of the human PRM1--> PRM2--> TNP2 domain using a PCR-based assay. The results show that this retained, enhanced DNase I sensitive domain reflects an enrichment of histones at discrete regions across the locus. In addition, a similar examination of other genes and repetitive sequences suggests the non-random distribution of histones and protamines within the sperm nucleus. A discussion of these results and their functional significance is presented.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Sequence-specific packaging of DNA in human sperm chromatin.

              The DNA in human sperm chromatin is packaged into nucleoprotamine (approximately 85%) and nucleohistone (approximately 15%). Whether these two chromatin fractions are sequence-specific subsets of the spermatozoon genome is the question addressed in this report. Sequence-specific packaging would suggest distinct structural and functional roles for the nucleohistone and nucleoprotamine in late spermatogenesis or early development or both. After removal of histones with 0.65M NaCl, exposed DNA was cleaved with Bam HI restriction endonuclease and separated by centrifugation from insoluble nucleoprotamine. The DNA sequence distribution of nucleohistone DNA in the supernatant and nucleoprotamine DNA in the pellet was compared by cloning size-selected single-copy sequences and by using the derived clones as probes of nucleohistone DNA and nucleoprotamine DNA. Two clones derived from nucleohistone DNA preferentially hybridized to nucleohistone DNA, and two clones derived from nucleoprotamine DNA preferentially hybridized to nucleoprotamine DNA, which demonstrated the existence of sequence-specific nucleohistone and nucleoprotamine components within the human spermatozoon.
                Bookmark

                Author and article information

                Journal
                Genome Biol
                Genome Biology
                BioMed Central
                1465-6906
                1465-6914
                2007
                26 September 2007
                : 8
                : 9
                : 227
                Affiliations
                [1 ]Biosciences and BioTechnology Division, Chemistry, Materials and Life Sciences, Lawrence Livermore National Laboratory, East Avenue, Livermore, CA 94550, USA
                Article
                gb-2007-8-9-227
                10.1186/gb-2007-8-9-227
                2375014
                17903313
                094f1f1d-2ceb-41e0-98a3-76a52c807d86
                Copyright © 2007 BioMed Central Ltd
                History
                Categories
                Protein Family Review

                Genetics
                Genetics

                Comments

                Comment on this article