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粗糙脉孢菌WC-1招募SWI/SNF来重塑频率并启动昼夜节律周期。

Neurospora WC-1 recruits SWI/SNF to remodel frequency and initiate a circadian cycle.

作者信息

Wang Bin, Kettenbach Arminja N, Gerber Scott A, Loros Jennifer J, Dunlap Jay C

机构信息

Department of Genetics, Geisel School of Medicine, Dartmouth, Hanover, New Hampshire, United States of America.

Department of Genetics, Geisel School of Medicine, Dartmouth, Hanover, New Hampshire, United States of America; Norris Cotton Cancer Center, Geisel School of Medicine, Dartmouth, Hanover, New Hampshire, United States of America.

出版信息

PLoS Genet. 2014 Sep 25;10(9):e1004599. doi: 10.1371/journal.pgen.1004599. eCollection 2014 Sep.

DOI:10.1371/journal.pgen.1004599
PMID:25254987
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4177678/
Abstract

In the negative feedback loop comprising the Neurospora circadian oscillator, the White Collar Complex (WCC) formed from White Collar-1 (WC-1) and White Collar-2 (WC-2) drives transcription of the circadian pacemaker gene frequency (frq). Although FRQ-dependent repression of WCC has been extensively studied, the mechanism by which the WCC initiates a circadian cycle remains elusive. Structure/function analysis of WC-1 eliminated domains previously thought to transactivate frq expression but instead identified amino acids 100-200 as essential for frq circadian expression. A proteomics-based search for coactivators with WCC uncovered the SWI/SNF (SWItch/Sucrose NonFermentable) complex: SWI/SNF interacts with WCC in vivo and in vitro, binds to the Clock box in the frq promoter, and is required both for circadian remodeling of nucleosomes at frq and for rhythmic frq expression; interestingly, SWI/SNF is not required for light-induced frq expression. These data suggest a model in which WC-1 recruits SWI/SNF to remodel and loop chromatin at frq, thereby activating frq expression to initiate the circadian cycle.

摘要

在由粗糙脉孢菌昼夜节律振荡器组成的负反馈回路中，由白领-1（WC-1）和白领-2（WC-2）形成的白领复合体（WCC）驱动昼夜节律起搏器基因频率（frq）的转录。尽管对WCC的FRQ依赖性抑制已进行了广泛研究，但WCC启动昼夜节律周期的机制仍不清楚。对WC-1的结构/功能分析消除了先前认为可反式激活frq表达的结构域，但反而确定了氨基酸100-200对frq昼夜节律表达至关重要。基于蛋白质组学寻找与WCC的共激活因子发现了SWI/SNF（开关/蔗糖非发酵）复合体：SWI/SNF在体内和体外与WCC相互作用，与frq启动子中的时钟框结合，并且对于frq处核小体的昼夜节律重塑和节律性frq表达都是必需的；有趣的是，光诱导的frq表达不需要SWI/SNF。这些数据提示了一种模型，其中WC-1招募SWI/SNF来重塑和环绕frq处的染色质，从而激活frq表达以启动昼夜节律周期。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b193/4177678/ee656089e6b0/pgen.1004599.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b193/4177678/03b466f8588e/pgen.1004599.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b193/4177678/bcee9bd69317/pgen.1004599.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b193/4177678/b421de8efff1/pgen.1004599.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b193/4177678/2d5b1b7cd8ac/pgen.1004599.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b193/4177678/ea3933aff868/pgen.1004599.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b193/4177678/8e2b813d1cd3/pgen.1004599.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b193/4177678/ee656089e6b0/pgen.1004599.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b193/4177678/03b466f8588e/pgen.1004599.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b193/4177678/bcee9bd69317/pgen.1004599.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b193/4177678/b421de8efff1/pgen.1004599.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b193/4177678/2d5b1b7cd8ac/pgen.1004599.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b193/4177678/ea3933aff868/pgen.1004599.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b193/4177678/8e2b813d1cd3/pgen.1004599.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b193/4177678/ee656089e6b0/pgen.1004599.g007.jpg

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