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基于转座酶可及染色质信号变化预测猪脂肪沉积过程中的关键肝脏转录因子

Prediction of essential liver transcription factors in response to fat deposition in pigs based on changes in transposase-accessible chromatin signals.

作者信息

Piórkowska Katarzyna, Żukowski Kacper, Kowalska Katarzyna, Ropka-Molik Katarzyna, Tyra Mirosław

机构信息

Animal Molecular Biology, National Research Institute of Animal Production, Cracow, Poland.

Department of Cattle Breeding, National Research Institute of Animal Production, Cracow, Poland.

出版信息

Anim Genet. 2025 Aug;56(4):e70032. doi: 10.1111/age.70032.

Abstract

Pigs have been altered throughout the decades to increase the meat content in their carcasses. However, this has led to a reduction in fat levels in subcutaneous, visceral, and intramuscular fats, where intramuscular fat is crucial for flavor. The current study used combined RNA-assay for transposase-accessible chromatin (ATAC) sequencing analysis to identify key transcription factors (TFs) that might regulate important molecular mechanisms associated with fat deposition in the livers of pigs. In this study, two native Złotnicka White pig groups were used that significantly differed in terms of their fat content. RNA-seq identified 272 genes as being differentially expressed (showing >1.2 fold change) and ATAC-seq identified 6333 significant peaks (differentially accessible regions [DARs]) in the transcription start site (TSS) flanking region. Ninety-eight genes overlapped between the RNA and ATAC seq results, and these differentially expressed genes-DARs were included in a subsequent motif analysis. The TRRUST and MEME tools were used to identify crucial TFs, which predicted possible binding TF motifs based on TSS ATAC peaks. The candidate TFs suggested in the present study for fat deposition in pigs are SREBP1, ATF4, KLF11, RORA, and MYC, whose DNA-binding motif sequence was enriched in DAR overlapping TSS. Moreover, for MYC, ATF4, and KLF11 TFs, DARs were identified within the TSS flanking regions. The present study aimed to pinpoint the key liver TFs that are indirectly related to fat deposition in pigs.

摘要

几十年来,猪一直在被改良,以增加其胴体中的肉含量。然而,这导致皮下、内脏和肌肉内脂肪中的脂肪水平降低,而肌肉内脂肪对风味至关重要。本研究使用结合RNA分析的转座酶可及染色质(ATAC)测序分析,以鉴定可能调控与猪肝脏脂肪沉积相关重要分子机制的关键转录因子(TFs)。在本研究中,使用了两个脂肪含量有显著差异的本地兹洛特尼卡白猪群体。RNA测序鉴定出272个基因存在差异表达(变化倍数>1.2倍),ATAC测序在转录起始位点(TSS)侧翼区域鉴定出6333个显著峰(差异可及区域 [DARs])。RNA和ATAC测序结果之间有98个基因重叠,这些差异表达基因-DARs被纳入后续的基序分析。使用TRRUST和MEME工具来鉴定关键TFs,它们基于TSS的ATAC峰预测可能的结合TF基序。本研究中提出的猪脂肪沉积候选TFs是SREBP1、ATF4、KLF11、RORA和MYC,其DNA结合基序序列在与TSS重叠的DAR中富集。此外,对于MYC、ATF4和KLF11 TFs,在TSS侧翼区域内鉴定出了DARs。本研究旨在确定与猪脂肪沉积间接相关的关键肝脏TFs。

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