Sperm-derived histones contribute to zygotic chromatin in humans
- Equal contributors
1 Department of Obstetrics and Gynaecology, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands
2 Division of Reproductive Medicine, Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Center, Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands
3 Nephrology Research Laboratory, Nijmegen Centre for Molecular Life Sciences, Division of Nephrology, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands
4 Carnegie Institution of Washington, Department of Embryology, 3520 San Martin Drive, Baltimore, MD 21218, USA
5 University Medical Center Utrecht, Department of Reproductive Medicine and Gynaecology,, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands
6 University Medical Center Utrecht, Department of Pharmacology and Anatomy, Rudolf Magnus Institute of Neuroscience, Universiteitsweg 100, 3584 CG, Utrecht, The Netherlands
BMC Developmental Biology 2008, 8:34 doi:10.1186/1471-213X-8-34Published: 31 March 2008
about 15% to 30% of the DNA in human sperm is packed in nucleosomes and transmission of this fraction to the embryo potentially serves as a mechanism to facilitate paternal epigenetic programs during embryonic development. However, hitherto it has not been established whether these nucleosomes are removed like the protamines or indeed contribute to paternal zygotic chromatin, thereby potentially contributing to the epigenome of the embryo.
to clarify the fate of sperm-derived nucleosomes we have used the deposition characteristics of histone H3 variants from which follows that H3 replication variants present in zygotic paternal chromatin prior to S-phase originate from sperm. We have performed heterologous ICSI by injecting human sperm into mouse oocytes. Probing these zygotes with an antibody highly specific for the H3.1/H3.2 replication variants showed a clear signal in the decondensed human sperm chromatin prior to S-phase. In addition, staining of human multipronuclear zygotes also showed the H3.1/H3.2 replication variants in paternal chromatin prior to DNA replication.
these findings reveal that sperm-derived nucleosomal chromatin contributes to paternal zygotic chromatin, potentially serving as a template for replication, when epigenetic information can be copied. Hence, the execution of epigenetic programs originating from transmitted paternal chromatin during subsequent embryonic development is a logical consequence of this observation.