Sperm Chromatin: Implications on organismal development and fertility

精子染色质：对有机体发育和生育能力的影响

• 批准号: 10450995
• 负责人: Saher Sue Hammoud
• 金额: $ 15.06万
• 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: 2021-07-19 至 2022-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10450995
• 关键词: Acetylation; Affect; Antibodies; Back; Binding; Biochemical; Biological; Biological Assay; Cell Nucleus; Cells; Chromatin; Code; Complex; Couples; Custom; DNA; Data; Deposition; Development; Diagnosis; 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; Longitudinal Studies; Lysine; Male Infertility; Mammals; Maps; Mass Spectrum Analysis; Modification; Molecular; Molecular Genetics; Mutant Strains Mice; Mutation; Oocytes; Outcome; Parents; Partner in relationship; Pattern; Phosphorylation; Post-Translational Protein Processing; Protamines; Proteins; Reagent; Reproductive Health; Role; Series; Serine; Site; Somatic Cell; Specificity; Spermatids; Spermatogenesis; System; Testing; Testis; Threonine; Transgenic Mice; Transgenic Organisms; Ursidae Family; Variant; egg; insight; male; male fertility; mouse model; novel; offspring; protamine 1; protein function; public health relevance; reproductive; sperm cell; sperm quality; tool; transgenerational epigenetic inheritance; zygote

Ancillary reproductive health projects to existing large and/or longitudinal studies 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, but the biological and functional significance of protamine protein packaging remains poorly understood. Here we identified a functional role for protamine proteins in coordinating proper embryonic development. This proposal aims to develop additional molecular genetic tools to dissect 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.

现有大型和/或纵向研究的辅助生殖健康项目 精子和卵细胞将遗传和表观遗传信息从父母传递给后代，充当两者之间的联系 一个物种的过去、现在和未来。与卵母细胞和体细胞不同，卵母细胞和体细胞将 DNA 包装成 组蛋白，成熟精子的 DNA 与鱼精蛋白结合，鱼精蛋白是一种高度碱性且快速进化的蛋白质， 对于父本染色质的压缩至关重要。这种差异化包装可以追溯到 5 亿年前， 但鱼精蛋白包装的生物学和功能意义仍然知之甚少。这里 我们确定了鱼精蛋白在协调适当胚胎发育中的功能作用。这 该提案旨在开发额外的分子遗传工具来剖析鱼精蛋白在生育力、早期生育中的作用。 发展、演变。总之，这里提出的发现将增加我们对以下分子的理解： 这些古老但快速进化的蛋白质可能会推翻长期以来对其假定功能的教条。