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Chd1的CHCT结构域与Rtf1之间的直接相互作用控制着Chd1在活性基因上的分布以及核小体定位。

A direct interaction between the Chd1 CHCT domain and Rtf1 controls Chd1 distribution and nucleosome positioning on active genes.

作者信息

Tripplehorn Sarah A, Shirra Margaret K, Lardo Santana M, Marvil Hannah G, Hainer Sarah J, Arndt Karen M

机构信息

Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA USA.

UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA USA.

出版信息

bioRxiv. 2024 Dec 6:2024.12.06.627179. doi: 10.1101/2024.12.06.627179.

Abstract

The nucleosome remodeler Chd1 is required for the re-establishment of nucleosome positioning in the wake of transcription elongation by RNA Polymerase II. Previously, we found that Chd1 occupancy on gene bodies depends on the Rtf1 subunit of the Paf1 complex in yeast. Here, we identify an N-terminal region of Rtf1 and the CHCT domain of Chd1 as sufficient for their interaction and demonstrate that this interaction is direct. Mutations that disrupt the Rtf1-Chd1 interaction result in an accumulation of Chd1 at the 5' ends of Chd1-occupied genes, increased cryptic transcription, altered nucleosome positioning, and concordant shifts in histone modification profiles. We show that a homologous region within mouse RTF1 interacts with the CHCT domains of mouse CHD1 and CHD2. This work supports a conserved mechanism for coupling Chd1 family proteins to the transcription elongation complex and identifies a cellular function for a domain within Chd1 about which little is known.

摘要

核小体重塑因子Chd1是RNA聚合酶II转录延伸后重新建立核小体定位所必需的。此前,我们发现酵母中基因体上的Chd1占据情况依赖于Paf1复合物的Rtf1亚基。在此,我们确定Rtf1的N端区域和Chd1的CHCT结构域足以实现它们之间的相互作用,并证明这种相互作用是直接的。破坏Rtf1-Chd1相互作用的突变会导致Chd1在其占据基因的5'端积累、隐蔽转录增加、核小体定位改变以及组蛋白修饰谱的相应变化。我们表明,小鼠RTF1内的一个同源区域与小鼠CHD1和CHD2的CHCT结构域相互作用。这项工作支持了一种将Chd1家族蛋白与转录延伸复合物偶联的保守机制,并确定了Chd1内一个鲜为人知的结构域的细胞功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1474/11643122/c912d1e10802/nihpp-2024.12.06.627179v1-f0001.jpg

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