Sperm Chromatin: Implications on organismal development and fertility

精子染色质：对有机体发育和生育力的影响

• 批准号: 10380089
• 负责人: Saher Sue Hammoud
• 金额: $ 41.67万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10380089
• 关键词: Acetylation; Affect; Antibodies; Back; Binding; Biochemical; Biochemical Genetics; Biological; Biological Assay; Biological Process; Cell Nucleus; Cells; Chromatin; Code; Complex; Couples; Custom; DNA; Data; Deposition; Development; Diagnosis; Elements; Embryo; Embryonic Development; Epigenetic Process; Epitopes; Etiology; Evolution; Excision; Fertility; Fertilization; Future; Genetic; Genetic Models; Genetic Transcription; Genome; Genomic Segment; Genomics; Hand; Histone Code; Histones; Immunofluorescence Immunologic; Infertility; Instruction; Intracytoplasmic Sperm Injections; Investigation; Link; Lysine; Male Infertility; Mammals; Maps; Mass Spectrum Analysis; Modification; Molecular; Mutant Strains Mice; Mutation; Oocytes; Outcome; Parents; Partner in relationship; Pattern; Phosphorylation; Post-Translational Protein Processing; Protamines; Proteins; Reagent; Role; Series; Serine; Site; Somatic Cell; Specificity; Spermatids; Spermatogenesis; System; Testing; Testis; Threonine; Transgenic Mice; Transgenic Organisms; Ursidae Family; Variant; egg; genetic approach; insight; male; male fertility; mouse model; novel; offspring; protamine 1; protein function; reproductive; sperm cell; sperm quality; transgenerational epigenetic inheritance; zygote

Sperm and egg cells carry genetic and epigenetic information from parents to offspring, serving as a link between the past, present and future of a species. Unlike oocytes and somatic cells, which package their DNA with histones, the DNA of mature sperm is bound by protamines, highly basic and rapidly evolving proteins that are essential for the compaction of paternal chromatin. This differential packaging traces back >500 million years, yet its biological and evolutionary significance remains unknown. Protamines have thus far been considered passive structural elements that hyper condense and protect paternal DNA, however emerging biochemical, evolutionary, and developmental evidence calls for a need to revisit protamine proteins’ biological function. We have employed cutting-edge molecular, biochemical, and genetic approaches to investigate the role of protamines in fertility, early development, and evolution. Together, the findings presented here will increase our molecular understanding of these ancient, yet rapidly evolving proteins and may overturn the long-held dogma of their presumed function.

精子和卵细胞将遗传和表观遗传信息从父母传递给后代，是连接一个物种的过去、现在和未来的纽带。与卵母细胞和体细胞用组蛋白包装DNA不同，成熟精子的DNA由蛋白蛋白结合，这是一种高度碱性和快速进化的蛋白质，对父系染色质的压缩至关重要。这种不同的包装可以追溯到5亿年前，但其生物学和进化意义尚不清楚。迄今为止，精蛋白一直被认为是过度浓缩和保护父系DNA的被动结构元件，然而，新出现的生物化学、进化和发育证据要求重新审视精蛋白的生物学功能。我们采用尖端的分子，生化和遗传方法来研究蛋白蛋白在生育，早期发育和进化中的作用。总之，这里提出的发现将增加我们对这些古老而迅速进化的蛋白质的分子理解，并可能推翻长期以来对其假定功能的教条。