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组蛋白修饰和转录因子的等位基因特异性结合不能预测相关 ChIP-seq 峰-外显子对的等位基因特异性表达。

Allele specific binding of histone modifications and a transcription factor does not predict allele specific expression in correlated ChIP-seq peak-exon pairs.

机构信息

Faculty of Veterinary & Agricultural Science, The University of Melbourne, Parkville, VIC, 3010, Australia.

Agriculture Victoria, AgriBio, Centre for AgriBiosciences, Bundoora, VIC, 3083, Australia.

出版信息

Sci Rep. 2023 Sep 20;13(1):15596. doi: 10.1038/s41598-023-42637-6.

Abstract

Allele specific expression (ASE) is widespread in many species including cows. Therefore, regulatory regions which control gene expression should show cis-regulatory variation which mirrors this differential expression within the animal. ChIP-seq peaks for histone modifications and transcription factors measure activity at functional regions and the height of some peaks have been shown to correlate across tissues with the expression of particular genes, suggesting these peaks are putative regulatory regions. In this study we identified ASE in the bovine genome in multiple tissues and investigated whether ChIP-seq peaks for four histone modifications and the transcription factor CTCF show allele specific binding (ASB) differences in the same tissues. We then investigate whether peak height and gene expression, which correlates across tissues, also correlates within the animal by investigating whether the direction of ASB in putative regulatory regions, mirrors that of the ASE in the genes they are putatively regulating. We found that ASE and ASB were widespread in the bovine genome but vary in extent between tissues. However, even when the height of a peak was positively correlated across tissues with expression of an exon, ASE of the exon and ASB of the peak were in the same direction only half the time. A likely explanation for this finding is that the correlations between peak height and exon expression do not indicate that the height of the peak causes the extent of exon expression, at least in some cases.

摘要

等位基因特异性表达 (ASE) 在许多物种中都很普遍,包括奶牛。因此,控制基因表达的调控区域应该表现出与动物体内这种差异表达相匹配的顺式调控变异。组蛋白修饰和转录因子的 ChIP-seq 峰测量功能区域的活性,并且一些峰的高度已被证明与特定基因的表达在组织间具有相关性,这表明这些峰是潜在的调控区域。在这项研究中,我们在多个组织中鉴定了牛基因组中的 ASE,并研究了四个组蛋白修饰和转录因子 CTCF 的 ChIP-seq 峰在相同组织中是否显示出等位基因特异性结合 (ASB) 的差异。然后,我们通过研究假定调节基因的 ASB 是否与它们所假定调节的基因的 ASE 方向一致,来研究峰高和基因表达在组织内是否具有相关性,这些表达在组织间具有相关性。我们发现 ASE 和 ASB 在牛基因组中广泛存在,但在不同组织之间存在程度差异。然而,即使峰的高度与外显子的表达在组织间呈正相关,外显子的 ASE 和峰的 ASB 也只有一半时间处于相同方向。这种发现的一个可能解释是,峰高和外显子表达之间的相关性并不表明峰高导致外显子表达的程度,至少在某些情况下是这样。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfdb/10511416/452793ea33a7/41598_2023_42637_Fig1_HTML.jpg

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