Ribosome biogenesis disruption mediated chromatin structure changes revealed by SRAtac, a customizable end to end analysis pipeline for ATAC-seq

核糖体生物合成破坏介导的染色质结构变化由 SRAtac 揭示,SRAtac 是一种可定制的 ATAC-seq 端到端分析流程

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作者:Trevor F Freeman, Qiuxia Zhao, Agustian Surya, Reed Rothe, Elif Sarinay Cenik

Abstract

The nucleolus is a large nuclear body that serves as the primary site for ribosome biogenesis. Recent studies have suggested that it also plays an important role in organizing chromatin architecture. However, to establish a causal relationship between nucleolar ribosome assembly and chromatin architecture, genetic tools are required to disrupt nucleolar ribosome biogenesis. In this study, we used ATAC-seq to investigate changes in chromatin accessibility upon specific depletion of two ribosome biogenesis components, RPOA-2 and GRWD-1, in the model organism Caenorhabditis elegans. To facilitate the analysis of ATAC-seq data, we introduced two tools: SRAlign, an extensible NGS data processing workflow, and SRAtac, a customizable end-to-end ATAC-seq analysis pipeline. Our results revealed highly comparable changes in chromatin accessibility following both RPOA-2 and GRWD-1 perturbations. However, we observed a weak correlation between changes in chromatin accessibility and gene expression. While our findings corroborate the idea of a feedback mechanism between ribosomal RNA synthesis, nucleolar ribosome large subunit biogenesis, and chromatin structure during the L1 stage of C. elegans development, they also prompt questions regarding the functional impact of these alterations on gene expression.

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