ScienceDaily (Aug. 3, 2009) — Scientists at Leeds and Bradford have discovered a unique ‘DNA signature’ in human sperm, which may act as a key that unlocks an egg’s fertility and triggers new life.
Drs David Miller and David Iles from the University of Leeds, in collaboration with Dr Martin Brinkworth at the University of Bradford, have found that sperm writes a DNA signature that can only be recognised by an egg from the same species. This enables fertilisation and may even explain how a species develops its own unique genetic identity.
Dr Iles says, “What we have discovered is a previously unrecognised DNA packaging ‘signature’ in mammalian sperm that may be essential for successful fertilisation of the egg and development of the embryo. We think it may also be ancient in origin.”
Without the right ‘key’, successful fertilisation either cannot occur, or if it does, development will not proceed normally. Notably, disturbances in human sperm DNA packaging are known to cause male infertility and pregnancy failures.
Scientists at Leeds and Bradford have discovered a unique ‘DNA signature’ in human sperm, which may act as a key that unlocks an egg’s fertility and triggers new life. (Credit: iStockphoto)
This ‘lock and key’ mechanism has other profound implications. Not only does it explain why some otherwise healthy men produce sperm that is sterile, but it also explains how different species evolve and retain their own identity.
Says Dr Miller, “Up until now, Doctors have struggled to understand idiopathic male infertility. Our latest research offers a plausible explanation for why some sperm malfunction or fail to function correctly.”
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Endonuclease-sensitive regions of human spermatozoal chromatin are highly enriched in promoter and CTCF binding sequences
Ali Arpanahi1, Martin Brinkworth2, David Iles3,7, Stephen A. Krawetz4, Agnieszka Paradowska5, Adrian E. Platts4, Myriam Saida1, Klaus Steger5, Philip Tedder6 and David Miller1,7
+Author Affiliations
1Reproduction and Early Development Unit, Leeds Institute of Genetics and Health Therapeutics, University of Leeds, Clarendon Way, Leeds LS2 9JT, United Kingdom;
2Biomedical Sciences, School of Life Sciences, University of Bradford, Bradford BD7 1DP, United Kingdom;
3Institute of Integrative and Comparative Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, United Kingdom;
4Department of Obstetrics and Gynecology, Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, Michigan 48201, USA;
5Department of Urology and Pediatric Urology, Justus Liebig University Giessen, Giessen 35385, Germany;
6Institute of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT, United Kingdom
Abstract
During the haploid phase of mammalian spermatogenesis, nucleosomal chromatin is ultimately repackaged by small, highly basic protamines to generate an extremely compact, toroidal chromatin architecture that is critical to normal spermatozoal function. In common with several species, however, the human spermatozoon retains a small proportion of its chromatin packaged in nucleosomes. As nucleosomal chromatin in spermatozoa is structurally more open than protamine-packaged chromatin, we considered it likely to be more accessible to exogenously applied endonucleases. Accordingly, we have used this premise to identify a population of endonuclease-sensitive DNA sequences in human and murine spermatozoa. Our results show unequivocally that, in contrast to the endonuclease-resistant sperm chromatin packaged by protamines, regions of increased endonuclease sensitivity are closely associated with gene regulatory regions, including many promoter sequences and sequences recognized by CCCTC-binding factor (CTCF). Similar differential packaging of promoters is observed in the spermatozoal chromatin of both mouse and man. These observations imply the existence of epigenetic marks that distinguish gene regulatory regions in male germ cells and prevent their repackaging by protamines during spermiogenesis. The ontology of genes under the control of endonuclease-sensitive regulatory regions implies a role for this phenomenon in subsequent embryonic development.
Footnotes
↵7 Corresponding authors.
E-mail d.miller@leeds.ac.uk; fax 44-113-343-7804.
E-mail d.e.iles@leeds.ac.uk; fax 44-113-343-4311.
[Supplemental material is available online at www.genome.org. The microarray data from this study have been submitted to NCBI Gene Expression Omnibus (GEO) (http://www.ncbi.nlm.nih.gov/geo/) under accession nos. GSM327832–GSM327833, GSM305271–GSM305280, GSM305091–GSM305092, GSM406528–GSM406531, and GSM394743.]
Article published online before print. Article and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.094953.109.
Received April 12, 2009.
Accepted May 27, 2009.
Copyright © 2009 by Cold Spring Harbor Laboratory Press
