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

基本信息

批准号：
10181153
负责人：
Saher Sue Hammoud
金额：
$ 40.4万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
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/10181153
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 Structure 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

项目摘要

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，充当物种过去、现在和未来之间的纽带，与用组蛋白包装 DNA 的卵母细胞和体细胞不同，成熟精子的 DNA 是通过组蛋白结合的。鱼精蛋白是一种高度碱性且快速进化的蛋白质，对于父系染色质的压缩至关重要，这种差异包装可以追溯到 5 亿年前，但迄今为止，鱼精蛋白的生物学和进化意义仍被认为是被动结构。然而，新出现的生化、进化和发育证据要求重新审视鱼精蛋白的生物学功能，我们采用了尖端的分子、生化和遗传学方法来研究鱼精蛋白在细胞中的作用。总之，这里提出的发现将增加我们对这些古老但快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。