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Sperm-derived histones contribute to zygotic chromatin in humans.

van der Heijden GW, Ramos L, Baart EB, van den Berg IM, Derijck AA, van der Vlag J, Martini E, de Boer P - BMC Dev. Biol. (2008)

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Obstetrics and Gynaecology, Radboud University Nijmegen Medical Centre, P,O, Box 9101, 6500 HB Nijmegen, The Netherlands. vanderheijden@ciwemb.edu

ABSTRACT

Background: 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.

Results: 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.

Conclusion: 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.

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Presence of histone H3 variants in human sperm. Human sperm, treated with heparin to induce chromatin decondensation, stained with a pan-H3 antibody (a), which recognizes all histone H3 variants (H3.1, H3.2 and H3.3) or a H3.1/H3.2-specific antibody (b) revealed for both antibodies a diffuse, global staining. The merge (c) with DAPI, which labels DNA, shows the nuclear localisation of the histones.
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Figure 1: Presence of histone H3 variants in human sperm. Human sperm, treated with heparin to induce chromatin decondensation, stained with a pan-H3 antibody (a), which recognizes all histone H3 variants (H3.1, H3.2 and H3.3) or a H3.1/H3.2-specific antibody (b) revealed for both antibodies a diffuse, global staining. The merge (c) with DAPI, which labels DNA, shows the nuclear localisation of the histones.

Mentions: Both the replacement and replication variants are detected in sperm by HPLC analysis [4]. To visualize histone H3 in sperm by immunofluorescence, we decondensed the cells by incubation in a mixture containing heparin and DTT. The dense structure of sperm chromatin does not allow antibody penetration without this treatment. Staining of decondensed sperm with the pan-H3 and H3.1/H3.2 antibodies showed a relatively homogeneous structure revealing signal for both (see Fig. 1).


Sperm-derived histones contribute to zygotic chromatin in humans.

van der Heijden GW, Ramos L, Baart EB, van den Berg IM, Derijck AA, van der Vlag J, Martini E, de Boer P - BMC Dev. Biol. (2008)

Presence of histone H3 variants in human sperm. Human sperm, treated with heparin to induce chromatin decondensation, stained with a pan-H3 antibody (a), which recognizes all histone H3 variants (H3.1, H3.2 and H3.3) or a H3.1/H3.2-specific antibody (b) revealed for both antibodies a diffuse, global staining. The merge (c) with DAPI, which labels DNA, shows the nuclear localisation of the histones.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2358879&req=5

Figure 1: Presence of histone H3 variants in human sperm. Human sperm, treated with heparin to induce chromatin decondensation, stained with a pan-H3 antibody (a), which recognizes all histone H3 variants (H3.1, H3.2 and H3.3) or a H3.1/H3.2-specific antibody (b) revealed for both antibodies a diffuse, global staining. The merge (c) with DAPI, which labels DNA, shows the nuclear localisation of the histones.
Mentions: Both the replacement and replication variants are detected in sperm by HPLC analysis [4]. To visualize histone H3 in sperm by immunofluorescence, we decondensed the cells by incubation in a mixture containing heparin and DTT. The dense structure of sperm chromatin does not allow antibody penetration without this treatment. Staining of decondensed sperm with the pan-H3 and H3.1/H3.2 antibodies showed a relatively homogeneous structure revealing signal for both (see Fig. 1).

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Obstetrics and Gynaecology, Radboud University Nijmegen Medical Centre, P,O, Box 9101, 6500 HB Nijmegen, The Netherlands. vanderheijden@ciwemb.edu

ABSTRACT

Background: 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.

Results: 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.

Conclusion: 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.

Show MeSH
Related in: MedlinePlus