精子染色质可访问性参与压力激素受体激活的代际效应
Vincent Fischer1,2, Miriam Kretschmer1,2, Pierre-Luc Germain1,3,4,5
1Laboratory of Epigenetics and Neuroendocrinology, Institute for Neuroscience, Department of Health Sciences and Technology, ETH Zürich, Zürich, Switzerland.
Translational psychiatry
|December 8, 2023
概括
父亲接触德甲会改变后代的表型,但不仅仅是通过精子RNA. 精子染色质可访问性的表观遗传变化与这些影响跨代传播有关.
科学领域:
- 表观遗传学和发育生物学
- 生殖生物学和毒理学
背景情况:
- 已知德克萨米他 (一种压力激素受体激动剂) 的父给药会影响后代的表型.
- 代际影响通常与精子RNA有关,但其他生殖系表观遗传修饰也很有可能.
- 以前的研究表明,精子RNA在传递环境诱导效应方面起着作用.
研究的目的:
- 为了研究改变精子RNAs在跨代传递德克萨梅他诱导的表型中的作用.
- 检查德克萨米他松对精子染色质可访问性的影响及其与后代基因表达的相关性.
- 探索DNA修饰,压力激素受体活性和精子染色质可访问性之间的关系.
主要方法:
- 从暴露于甲基的雄性精子中注射精子RNA到原始卵子细胞中,然后进行后代的表型化.
- ATAC测序用于评估德克萨米他暴露后精子中的染色质可访问性变化.
- 定量逆转录PCR (q-RT-PCR) 用于分析后代组织中的基因表达.
- 通过降低丁氨酸-DNA糖酶水平来研究其对染色质可访问性和受体活性的影响来进行基因操纵.
主要成果:
- 从注射精子RNA中观察到的后代的表型变化与使用暴露男性精子进行体外受精时的变化不一致,这表明RNA不是唯一的调解者.
- 德克萨米他暴露显著改变了精子中的特定基因组特征和基因调控位点上的染色质可访问性.
- 在后代组织中观察到基因表达的改变,与精子染色质可访问性的变化相关.
- 在特定的DNA修改,压力激素受体活性和精子染色质可访问性之间建立了相关性.
- 降低乙氨基-DNA糖酶水平导致染色质可访问性和压力激素受体活性同时发生变化.
结论:
- 精子RNA不是德克萨米他诱导的代际表型效应的唯一媒介.
- 甲暴露会诱导精子染色质可访问性的表观遗传修饰,这有助于改变后代的表型.
- DNA修饰和压力激素受体活性与精子染色质可访问性有关,这代表了跨代遗传的潜在机制.
更多相关视频
相关概念视频
Inheritance of Chromatin Structures
6.3K
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...
6.3K
Spermatogenesis
102.5K
Spermatogenesis is the process by which haploid sperm cells are produced in the male testes. It starts with stem cells located close to the outer rim of seminiferous tubules. These spermatogonial stem cells divide asymmetrically to give rise to additional stem cells (meaning that these structures “self-renew”), as well as sperm progenitors, called spermatocytes. Importantly, this method of asymmetric mitotic division maintains a population of spermatogonial stem cells in the male...
102.5K
Chromatin Structure Regulates pre-mRNA Processing
7.0K
In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
The chromatin structure, especially...
The chromatin structure, especially...
7.0K
Epigenetic Regulation
3.0K
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...
3.0K
Chromatin Position Affects Gene Expression
23.3K
Chromatin is the massive complex of DNA and proteins packaged inside the nucleus. The complexity of chromatin folding and how it is packaged inside the nucleus greatly influences access to genetic information. Generally, the nucleus' periphery is considered transcriptionally repressive, while the cell's interior is considered a transcriptionally active area.
Topologically Associated Domains (TADs)
The 3-dimensional positioning of chromatin in the nucleus influences the...
Topologically Associated Domains (TADs)
The 3-dimensional positioning of chromatin in the nucleus influences the...
23.3K
Chromatin Modification in iPS Cells
1.7K
Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (iPS) cells.
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
1.7K


