Are protamines involved in higher condensation of sperm nuclear chromatin responsible for epigenomic information?

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K21360
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 42:Veterinary medical science, animal science, and related fields
• Research Institution: University of Tsukuba
• Principal Investigator: Tanimoto Keiji 筑波大学, 生命環境系, 教授 (90261776)
• Project Period (FY): 2020-07-30 – 2024-03-31
• Keywords: エピゲノム / 精子 / プロタミン / アルギニンメチル化 / PRMT1

Outline of Final Research Achievements

We hypothesized that protamine, which is abundant in sperm chromatin and contains many arginine residues, might be a novel (non-DNA) carrier of genetic information that is inherited from parents (gametes) to their children, and explored the possibility that its chemical modification functions as epigenome information and its role in early development after fertilization. While we found that protamine is methylated by protein arginine methyltransferase (PRMT) in vitro, we found no clear evidence of modification in mammalian cells. Therefore, we deleted the PRMT1 gene in a sperm-specific manner and found partial fertility, which differed from the findings previously reported. After IVF, however, almost half of the embryos seemed abnormal in shape. It's not clear whether the methylation defect of protamine is involved in this phenotype.

Free Research Field

エピジェネティクス

Academic Significance and Societal Importance of the Research Achievements

近年、親が曝された環境要因（栄養状態、精神的ストレス、化学物質等）が、次世代（疾患の罹患率など）に影響を与える例が、疫学調査やモデル動物を用いた実験から示されている。これは、配偶子に生じたエピジェネティックな変化が、次世代での遺伝子発現を変化させた結果であると考えられている。これまで、変化の主体はDNAメチル化やヒストンの化学修飾が考えられてきた。精子プロタミンの翻訳後修飾が遺伝情報担体として機能することが分かれば、親から子へ継承されるエピゲノム研究に新たな次元を与える重要な発見となる。