特定的DNMT3C侧面序列偏好有助于年轻小鼠逆转移子的甲基化
Leonie Dossmann1, Max Emperle1, Michael Dukatz1
1Institute of Biochemistry and Technical Biochemistry, Department of Biochemistry, University of Stuttgart, Allmandring 31, 70569, Stuttgart, Germany.
Communications biology
|May 16, 2024
概括
基因甲基转移酶DNMT3C对于沉默男性生殖系中的年轻逆转移子是必不可少的,它表现出独特的序列偏好. 这些偏好促进了特定的小鼠逆转移体的甲基化,有助于基因组的稳定性.
科学领域:
- 表观遗传学和基因组学
- 哺乳动物分子生物学
- 进化生物学 进化生物学
背景情况:
- 基因甲基转移酶 (DNMTs) 在表观遗传调节中起着至关重要的作用.
- DNMT3C是 muroids 中 DNMT3B 的复制物,对于生殖线逆转移素沉默至关重要.
- 了解DNMT3C的基底特异性是其在基因组防御中的功能关键.
研究的目的:
- 为了研究DNMT3C.的侧边序列偏好.
- 为了确定DNMT3C独特的基质识别的分子基础.
- 阐明DNMT3C在逆转移子和表观遗传防御的共同进化中的作用.
主要方法:
- 利用专门的测试系统来确定DNMT3C侧面序列偏好.
- 在催化领域中确定了特定的氨基酸 (C543,V547) 负责这些偏好.
- 重新分析了已发表的数据,并对目标逆转移子序列的DNMT3C活性进行了实验验证.
主要成果:
- DNMT3C在-2和-1侧面显示独特的细胞因子偏好,与其他DNMT3酶不同.
- 两个氨基酸,C543和V547,负责这些特定物种的偏好,并被保存在壁状物质中.
- DNMT3C的偏好的侧翼序列富含年轻的小鼠逆转移子,它们是它的生物标.
- DNMT3C在这些逆转移子标产生的基质上表现出较高的甲基化活性.
结论:
- DNMT3C的侧面序列偏好与年轻的小鼠逆转移子精确匹配,促进它们的甲基化和沉默.
- 这种特异性为反转移子和哺乳动物表观遗传防御系统的共同进化提供了机械的见解.
- 这些发现凸显了DNMT3C在通过向抑制逆转移素来维持哺乳动物的基因组稳定性方面的关键作用.
相关概念视频
Non-LTR Retrotransposons
11.5K
As the name suggests, non-LTR retrotransposons lack the long terminal repeats characteristic of the LTR retrotransposons. Additionally, both LTR and non-LTR retrotransposons use distinct mechanisms of mobilization. Non-LTR retrotransposons are further divided into two classes - Long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs), both of which occur abundantly in most mammals, including humans. Some of the active non-LTR retrotransposons in humans are L1...
11.5K
LTR Retrotransposons
17.5K
LTR retrotransposons are class I transposable elements with long terminal repeats flanking an internal coding region. These elements are less abundant in mammals compared to other class I transposable elements. About 8 percent of human genomic DNA comprises LTR retrotransposons. Some of the common examples of LTR retrotransposons are Ty elements in yeast and Copia elements in Drosophila.
The internal coding region of LTR retrotransposons and their mechanism of transposition closely resembles a...
The internal coding region of LTR retrotransposons and their mechanism of transposition closely resembles a...
17.5K
DNA-only Transposons
14.5K
DNA-only transposons are called autonomous transposons since they code for the enzyme transposase that is required for the transposition mechanism. Insertion of transposons can alter gene functions in multiple ways. They can mutate the gene, alter gene expression by introducing a novel promoter or insulator sequence, introduce new splice sites, and change the mRNA transcripts produced, or remodel chromatin structure.
The donor site from where the transposon is excised is either degraded or...
The donor site from where the transposon is excised is either degraded or...
14.5K
Conservative Site-specific Recombination and Phase Variation
6.0K
Because the DNA segments are cut and reorganized in a direction-specific manner, site-specific recombination has emerged as an efficient genetic engineering technique. Flippase and Cyclization recombinases or Flp and Cre, respectively, are two members of the tyrosine recombinase family derived from bacteriophages, that are used to mediate site-specific DNA insertions, deletions, and targeted expression of proteins in mammalian cell lines.
The recognition sites for Cre recombinase called LoxP...
The recognition sites for Cre recombinase called LoxP...
6.0K
Overview of Transposition and Recombination
15.4K
Transposons make up a significant part of genomes of various organisms. Therefore, it is believed that transposition played a major evolutionary role in speciation by changing genome sizes and modifying gene expression patterns. For example, in bacteria, transposition can lead to conferring antibiotic resistance. Movement of transposable elements within the genetic pool of pathogenic bacteria can aid in transfer of antibiotic-resistant genetic elements. In eukaryotes, transposons can carry out...
15.4K
piRNA - Piwi-interacting RNAs
6.8K
PIWI-interacting RNAs, or piRNAs, are the most abundant short non-coding RNAs. More than 20,000 genes have been found in humans that code for piRNAs while only 2000 genes have been found for miRNAs. piRNAs can act at the transcriptional and post-transcriptional levels and have a vital role in silencing transposable elements present in germ cells. They are also involved in epigenetic silencing and activation. Previously, they were thought to function only in germ cells but new evidence suggests...
6.8K


