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Reproduction Abstracts (2016) 3 P004 | DOI: 10.1530/repabs.3.P004

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The function of Histone Variants in female infertility

Chih-Jen Lin

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MRC Centre for Reproductive Health, University of Edinburgh, UK.


Histone variants can replace canonical histones in the nucleosome and modify chromatin structure and gene expression. The histone variant H3.3 preferentially associates with active chromatin and has been implicated in the regulation of a diverse range of developmental processes. We recently showed that maternal Hira, a chaperone for the histone variant H3.3, is required for mouse development past the zygote stage. Male pronucleus formation is inhibited upon deletion of Hira due to a lack of nucleosome assembly in the sperm genome. Hira mutant oocytes are incapable of developing parthenogenetically, indicative of a role for Hira in the female genome. Our results demonstrate that Hira-mediated H3.3 incorporation is essential for parental genome reprogramming and reveal an unexpected role for rRNA transcription in the mouse zygote. In addition, we also reported that the specific knockdown of H3.3 in fertilized mouse zygotes leads to developmental arrest at the morula stage. Loss of H3.3 leads to over-condensation and mis-segregation of chromosomes as early as the two-cell stage, with corresponding high levels of aneuploidy. H3.3-deficient embryos have significantly reduced levels of markers of open chromatin, such as H3K36me2 and H4K16Ac. In addition, H3.3 KD embryos have increased incorporation of linker H1. These results reveal that H3.3 mediates a balance between open and condensed chromatin that is crucial for the fidelity of chromosome segregation during early mouse development. In summary, Hira-mediated H3.3 incorporation is essential for mouse early embryo development. Further investigation will focus on dissection of its roles in female infertility and the mechanisms of ribosomal RNA transcription.

Volume 3

Society for Reproduction and Fertility Annual Conference 2016

Winchester, UK
11 Jul 2016 - 11 Jul 2016

Society for Reproduction and Fertility 

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