Insertion of short L1 sequences generates inter-strain histone acetylation differences in the mouse.

IF 4.7 2区 生物学 Q1 GENETICS & HEREDITY
Beverly Ann G Boyboy, Kenji Ichiyanagi
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引用次数: 0

Abstract

Background: Gene expression divergence between populations and between individuals can emerge from genetic variations within the genes and/or in the cis regulatory elements. Since epigenetic modifications regulate gene expression, it is conceivable that epigenetic variations in cis regulatory elements can also be a source of gene expression divergence.

Results: In this study, we compared histone acetylation (namely, H3K9ac) profiles in two mouse strains of different subspecies origin, C57BL/6 J (B6) and MSM/Ms (MSM), as well as their F1 hybrids. This identified 319 regions of strain-specific acetylation, about half of which were observed between the alleles of F1 hybrids. While the allele-specific presence of the interferon regulatory factor 3 (IRF3) binding sequence was associated with allele-specific histone acetylation, we also revealed that B6-specific insertions of a short 3' fragment of LINE-1 (L1) retrotransposon occur within or proximal to MSM-specific acetylated regions. Furthermore, even in hyperacetylated domains, flanking regions of non-polymorphic 3' L1 fragments were hypoacetylated, suggesting a general activity of the 3' L1 fragment to induce hypoacetylation. Indeed, we confirmed the binding of the 3' region of L1 by three Krüppel-associated box domain-containing zinc finger proteins (KZFPs), which interact with histone deacetylases. These results suggest that even a short insertion of L1 would be excluded from gene- and acetylation-rich regions by natural selection. Finally, mRNA-seq analysis for F1 hybrids was carried out, which disclosed a link between allele-specific promoter/enhancer acetylation and gene expression.

Conclusions: This study disclosed a number of genetic changes that have changed the histone acetylation levels during the evolution of mouse subspecies, a part of which is associated with gene expression changes. Insertions of even a very short L1 fragment can decrease the acetylation level in their neighboring regions and thereby have been counter-selected in gene-rich regions, which may explain a long-standing mystery of discrete genomic distribution of LINEs and SINEs.

插入短 L1 序列会导致小鼠不同品系间组蛋白乙酰化的差异。
背景:种群之间和个体之间的基因表达差异可能来自基因内部和/或顺式调控元件的遗传变异。由于表观遗传修饰调控基因表达,可以想象顺式调控元件中的表观遗传变异也可能是基因表达差异的一个来源:在这项研究中,我们比较了两个不同亚种来源的小鼠品系--C57BL/6 J(B6)和MSM/Ms(MSM)以及它们的F1杂交种--的组蛋白乙酰化(即H3K9ac)谱。结果发现了 319 个品系特异性乙酰化区域,其中约一半是在 F1 杂交种的等位基因之间观察到的。虽然干扰素调节因子 3(IRF3)结合序列的等位基因特异性存在与等位基因特异性组蛋白乙酰化有关,但我们还发现,LINE-1(L1)反转座子短 3' 片段的 B6 特异性插入发生在 MSM 特异性乙酰化区域内或附近。此外,即使在高乙酰化区域,非多态性 3' L1 片段的侧翼区域也是低乙酰化的,这表明 3' L1 片段具有诱导低乙酰化的一般活性。事实上,我们证实了 L1 的 3' 区域与三个含 Krüppel-associated box domain 的锌指蛋白(KZFPs)的结合,这些锌指蛋白与组蛋白去乙酰化酶相互作用。这些结果表明,在自然选择的作用下,即使是短时间插入的 L1 也会被排除在基因和乙酰化富集区之外。最后,对 F1 杂交种进行了 mRNA-seq 分析,揭示了等位基因特异性启动子/增强子乙酰化与基因表达之间的联系:这项研究揭示了小鼠亚种进化过程中改变组蛋白乙酰化水平的一系列遗传变化,其中一部分与基因表达变化有关。即使是很短的L1片段的插入也会降低其邻近区域的乙酰化水平,从而在基因丰富的区域进行反选择,这可能解释了长期以来LINE和SINE在基因组中的离散分布之谜。
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来源期刊
Mobile DNA
Mobile DNA GENETICS & HEREDITY-
CiteScore
8.20
自引率
6.10%
发文量
26
审稿时长
11 weeks
期刊介绍: Mobile DNA is an online, peer-reviewed, open access journal that publishes articles providing novel insights into DNA rearrangements in all organisms, ranging from transposition and other types of recombination mechanisms to patterns and processes of mobile element and host genome evolution. In addition, the journal will consider articles on the utility of mobile genetic elements in biotechnological methods and protocols.
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