SMARCA5-DMRT1先驱综合体建立了表观遗传原始,以引导男性生殖线的发展
Yuka Kitamura1,2, Yasuhisa Munakata1,2,3, Hironori Abe1,4
1Department of Microbiology and Molecular Genetics, University of California, Davis, Davis, CA, 95616, USA.
bioRxiv : the preprint server for biology
|August 21, 2025
概括
通过创建可访问的DNA区域,染色体重塑剂SMARCA5对于男性生殖系的分化至关重要. 这种表观遗传启动了对精子发育至关重要的视网膜酸信号.
科学领域:
- 表观遗传学
- 发育生物学
- 细胞生物学
背景情况:
- 细胞类型特定的染色体景观对于细胞身份至关重要,但它们的形成尚未得到充分理解.
- 染色体重塑剂在建立这些景观中的作用,特别是在生殖细胞发育中,需要进一步研究.
研究的目的:
- 研究染色体重塑剂SMARCA5在男性生殖系分化的表观遗传特征中的作用.
- 阐明SMARCA5促进视网膜酸 (RA) 诱导的精子生成的机制.
主要方法:
- 在小鼠中,细菌细胞特异性的Smarca5基因被删除.
- 对分化精子种群的分析.
- 染色体可访问性测试
- 对基因调节元件的SMARCA5和DMRT1相互作用的研究.
主要成果:
- 细菌细胞特异性的Smarca5删除导致完全失去分化精子,模仿维生素A缺乏.
- 在围产期过渡期间,SMARCA5被调用到DMRT1结合部位,在增强剂和促进剂上建立可访问的染色体.
- 这些可访问的位点作为视网膜酸受体 (RAR) 的结合点,使RA诱导的分化成为可能.
结论:
- SMARCA5 建立了视网膜酸诱导的男性生殖线分化所必需的表观遗传原始.
- 发现了一种将先驱转录因子DMRT1活动与SMARCA5与外部信号响应 (RA) 联系起来的机制.
- 这项研究提供了关于如何调节染色体可访问性以允许发育信号通路的见解.
相关概念视频
Methods of Nuclear Reprogramming
1.9K
Nuclear reprogramming is a process of transforming one cell type into an unrelated cell type by epigenetic changes that alter the cell’s original gene expression pattern. Such epigenetic changes force cells to express a different set of genes, which play a significant role in inducing transformation into other cell types. Nuclear reprogramming offers applications in reproductive cloning for livestock propagation and regenerative medicine — developing patient-specific cells for...
1.9K
Genomic Imprinting and Inheritance
35.2K
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...
35.2K
Epigenetic Regulation
31.4K
Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
31.4K
Inheritance of Chromatin Structures
6.6K
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...
6.6K
Meiosis I
41.3K
Meiosis is the division of a diploid cell into haploid cells forming sperm and eggs in animals through differentiation. Meiosis I is the first stage of meiosis, where the genetic recombination of homologous chromosomes and the reduction of the ploidy level by half occurs.
Prophase I is the most extended and complex step of meiosis I characterized by synapsis, chromosome pairing, and recombination of the homologous chromosomes. This process is facilitated by a proteinaceous structure called the...
Prophase I is the most extended and complex step of meiosis I characterized by synapsis, chromosome pairing, and recombination of the homologous chromosomes. This process is facilitated by a proteinaceous structure called the...
41.3K
Spermatogenesis
103.4K
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...
103.4K


