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SWI/SNF 和 RSC 合作将高度表达基因的启动子核小体重新定位并逐出。

SWI/SNF and RSC cooperate to reposition and evict promoter nucleosomes at highly expressed genes in yeast.

机构信息

Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.

Division of Developmental Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.

出版信息

Genes Dev. 2018 May 1;32(9-10):695-710. doi: 10.1101/gad.312850.118. Epub 2018 May 21.

Abstract

The nucleosome remodeling complex RSC functions throughout the yeast genome to set the positions of -1 and +1 nucleosomes and thereby determines the widths of nucleosome-depleted regions (NDRs). The related complex SWI/SNF participates in nucleosome remodeling/eviction and promoter activation at certain yeast genes, including those activated by transcription factor Gcn4, but did not appear to function broadly in establishing NDRs. By analyzing the large cohort of Gcn4-induced genes in mutants lacking the catalytic subunits of SWI/SNF or RSC, we uncovered cooperation between these remodelers in evicting nucleosomes from different locations in the promoter and repositioning the +1 nucleosome downstream to produce wider NDRs-highly depleted of nucleosomes-during transcriptional activation. SWI/SNF also functions on a par with RSC at the most highly transcribed constitutively expressed genes, suggesting general cooperation by these remodelers for maximal transcription. SWI/SNF and RSC occupancies are greatest at the most highly expressed genes, consistent with their cooperative functions in nucleosome remodeling and transcriptional activation. Thus, SWI/SNF acts comparably with RSC in forming wide nucleosome-free NDRs to achieve high-level transcription but only at the most highly expressed genes exhibiting the greatest SWI/SNF occupancies.

摘要

核小体重塑复合物 RSC 在整个酵母基因组中发挥作用,以确定 -1 和 +1 核小体的位置,从而决定核小体缺失区域 (NDR) 的宽度。相关复合物 SWI/SNF 参与某些酵母基因的核小体重塑/逐出和启动子激活,包括转录因子 Gcn4 激活的基因,但似乎没有广泛参与建立 NDR。通过分析缺乏 SWI/SNF 或 RSC 催化亚基的突变体中大量 Gcn4 诱导基因,我们发现这些重塑因子在从启动子的不同位置逐出核小体并重新定位 +1 核小体下游以产生更宽的 NDR(高度缺乏核小体)方面存在合作在转录激活过程中。SWI/SNF 还可以与 RSC 在转录最活跃的组成型表达基因上发挥同等作用,这表明这些重塑因子通常会进行合作以实现最大转录。SWI/SNF 和 RSC 的占有率在转录最活跃的基因上最高,这与它们在核小体重塑和转录激活中的合作功能一致。因此,SWI/SNF 与 RSC 类似,形成广泛的无核小体 NDR 以实现高水平转录,但仅在表达最高的基因上,SWI/SNF 的占有率最高。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6243/6004078/d9a0683344a1/695f01.jpg

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