Coronado-Zamora Marta, González Josefa
Institut Botànic de Barcelona, CSIC, CMCNB, Barcelona, Spain.
Genome Biol. 2025 Aug 18;26(1):251. doi: 10.1186/s13059-025-03705-4.
Transposable elements (TEs) represent a threat to genome integrity due to their proliferative capacity. Eukaryotic cells silence TEs through different molecular mechanisms, including the deposition of repressive histone marks. Previous studies have shown that TE repressive marks can spread to neighboring sequences. However, evidence for this spreading leading to nearby gene silencing remains limited. Similarly, whether TEs induce changes in the enrichment of active histone marks genome-wide, and the potential impact on gene expression have not been widely studied.
In this work, we perform a comprehensive study of the epigenetic effects of 2235 TEs and their potential effects on nearby gene expression on Drosophila melanogaster head, gut, and ovary. While most TEs (816) induce the enrichment of the H3K9me3 repressive mark, with stronger epigenetic effects in the ovary, a substantial number (345 TEs) induce the enrichment of the H3K27ac active mark, particularly in the gut. We find that 70% of the H3K9me3 enriched TEs associated with expression changes downregulate the nearby gene, and 50% of the H3K27ac enriched TEs associated with expression changes lead to gene upregulation. These changes in expression affect specific regulatory networks only in the head. Furthermore, TE epigenetic effects on gene expression are genomic context dependent. Finally, we find that 221 TEs also affect gene expression by disrupting regions enriched for histone marks. CONCLUSIONS: Overall, our results show that TEs contribute to the generation of regulatory novelty through epigenetic changes, with these epigenetic effects not restricted to gene silencing and being genomic context dependent.
转座元件(TEs)因其增殖能力对基因组完整性构成威胁。真核细胞通过不同的分子机制使TEs沉默,包括抑制性组蛋白标记的沉积。先前的研究表明,TE抑制标记可扩散至邻近序列。然而,这种扩散导致附近基因沉默的证据仍然有限。同样,TEs是否会在全基因组范围内引起活性组蛋白标记富集的变化以及对基因表达的潜在影响尚未得到广泛研究。
在这项工作中,我们对2235个TEs在黑腹果蝇头部、肠道和卵巢中的表观遗传效应及其对附近基因表达的潜在影响进行了全面研究。虽然大多数TEs(816个)诱导H3K9me3抑制标记的富集,在卵巢中具有更强的表观遗传效应,但相当数量的TEs(345个)诱导H3K27ac活性标记的富集,特别是在肠道中。我们发现,70%与表达变化相关的H3K9me3富集TEs会下调附近基因,50%与表达变化相关的H3K27ac富集TEs会导致基因上调。这些表达变化仅在头部影响特定的调控网络。此外,TEs对基因表达的表观遗传效应取决于基因组背景。最后,我们发现221个TEs还通过破坏富含组蛋白标记的区域来影响基因表达。
总体而言,我们的结果表明,TEs通过表观遗传变化促进了调控新特性的产生,这些表观遗传效应不仅限于基因沉默,且取决于基因组背景。