在发育中的精子中基素甲基化的破坏会对后代的健康造成影响
Keith Siklenka1, Serap Erkek2, Maren Godmann3
1Department of Pharmacology and Therapeutics, Faculty of Medicine, McGill University, Montreal, Quebec, Canada.
概括
父亲表观遗传可能会影响后代的发育. 在精子中过度表达基因组甲基酶KDM1A导致跨代健康缺陷,突出表现出精子表观遗传.
科学领域:
- 表观遗传学
- 发育生物学
- 生殖科学
背景情况:
- 父亲因素影响后代的健康和发育.
- 父亲表观遗传的机制尚未完全理解.
- 精子核细胞在表观遗传中的作用尚不清楚.
研究的目的:
- 调查基因组脱甲酶KDM1A在父表观遗传中的作用.
- 确定精子中的KDM1A活性是否影响后代的发育和生存能力.
- 探索变化的精子表观遗传学的跨代效应.
主要方法:
- 在精子生成过程中产生过度表达KDM1A的转基因小鼠.
- 在精子中分析基因组修饰 (H3K4二甲基化).
- 评估后代的发育,生存能力和RNA概况.
- 检查了CpG丰富区域的DNA甲基化.
主要成果:
- 精子中的KDM1A过度表达减少了H3K4二甲基化.
- 过度表达KDM1A的父亲的后代表现出发育和生存能力受损.
- 这些缺陷是跨代的,在没有KDM1A生殖系表达的情况下持续存在.
- 在精子和后代中观察到改变的RNA概况.
- 没有检测到CpG丰富区域的DNA甲基化变化.
结论:
- 发展中的精子中的基因组脱甲酶活性可以启动发育缺陷的表观遗传.
- 在CpG位点的DNA甲基化没有变化的情况下,表观遗传会发生.
- 精子表观遗传学受到KDM1A等因素的影响,在跨代健康结果中起着关键作用.
更多相关视频
相关概念视频
Genomic Imprinting and Inheritance
38.7K
Diploid organisms inherit genetic material through chromosomes from both parents. Copies of the same gene are known as alleles. In most cases, both alleles are simultaneously expressed and allow various cellular processes to function optimally. If one of the alleles is missing or mutated, the expression of the other allele can compensate; however, this is not true for all genes.
The expression of some genes depends on which parent passed the gene to the offspring, through a phenomenon known as...
The expression of some genes depends on which parent passed the gene to the offspring, through a phenomenon known as...
38.7K
Epigenetic Regulation
4.2K
Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
X-chromosome...
4.2K
Epigenetic Regulation
34.3K
Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
34.3K
Inheritance of Chromatin Structures
7.9K
Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying...
7.9K
Nucleosome Remodeling
11.6K
Nucleosomes are the basic units of chromatin compaction. Each nucleosome consists of the DNA bound tightly around a histone core, which makes the DNA inaccessible to DNA binding proteins such as DNA polymerase and RNA polymerase. Hence, the fundamental problem is to ensure access to DNA when appropriate, despite the compact and protective chromatin structure.
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
11.6K
Spreading of Chromatin Modifications
10.0K
The histone proteins in the nucleosomes are post-translationally modified (PTM) to increase or decrease access to DNA. The commonly observed PTMs are methylation, acetylation, phosphorylation, and ubiquitination of lysine amino acids in the histone H3 tail region. These histone modifications have specific meaning for the cell. Hence, they are called "histone code". The protein complex involved in histone modification is termed as "reader-writer" complex.
Writers
The writer...
Writers
The writer...
10.0K


