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多药耐药转录因子 Pdr1p 和 Pdr3p 的活性受结合位点侧翼序列的调节。

Activity of the pleiotropic drug resistance transcription factors Pdr1p and Pdr3p is modulated by binding site flanking sequences.

机构信息

Department of Molecular Biosciences, Northwestern University, Evanston, Illinois, USA.

出版信息

FEBS Lett. 2024 Jan;598(2):169-186. doi: 10.1002/1873-3468.14762. Epub 2023 Nov 8.

DOI:10.1002/1873-3468.14762
PMID:37873734
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10843404/
Abstract

The transcription factors Pdr1p and Pdr3p regulate pleiotropic drug resistance (PDR) in Saccharomyces cerevisiae via the PDR responsive elements (PDREs) to modulate gene expression. However, the exact mechanisms underlying the differences in their regulons remain unclear. Employing genomic occupancy profiling (CUT&RUN), binding assays, and transcription studies, we characterized the differences in sequence specificity between transcription factors. Findings reveal distinct preferences for core PDRE sequences and the flanking sequences for both proteins. While flanking sequences moderately alter DNA binding affinity, they significantly impact Pdr1/3p transcriptional activity. Notably, both proteins demonstrated the ability to bind half sites, showing potential enhancement of transcription from adjacent PDREs. This insight sheds light on ways Pdr1/3p can differentially regulate PDR.

摘要

转录因子 Pdr1p 和 Pdr3p 通过 PDR 响应元件 (PDRE) 调节酿酒酵母中的多药耐药性 (PDR)，从而调节基因表达。然而，它们调控基因表达的具体机制仍不清楚。我们采用基因组占据谱分析 (CUT&RUN)、结合测定和转录研究，对转录因子之间的序列特异性差异进行了表征。研究结果揭示了这两种蛋白对核心 PDRE 序列和侧翼序列的不同偏好。虽然侧翼序列会适度改变 DNA 结合亲和力，但它们会显著影响 Pdr1/3p 的转录活性。值得注意的是，这两种蛋白都能够结合半位点，表明它们能够增强来自相邻 PDRE 的转录。这一发现揭示了 Pdr1/3p 可以差异化调节 PDR 的方式。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53cc/10843404/329ca6c76758/nihms-1939035-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53cc/10843404/e9b6debcdce6/nihms-1939035-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53cc/10843404/25897f207695/nihms-1939035-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53cc/10843404/3300ad7b1479/nihms-1939035-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53cc/10843404/552edc56821d/nihms-1939035-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53cc/10843404/b5dc15e907bd/nihms-1939035-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53cc/10843404/329ca6c76758/nihms-1939035-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53cc/10843404/e9b6debcdce6/nihms-1939035-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53cc/10843404/25897f207695/nihms-1939035-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53cc/10843404/3300ad7b1479/nihms-1939035-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53cc/10843404/552edc56821d/nihms-1939035-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53cc/10843404/b5dc15e907bd/nihms-1939035-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53cc/10843404/329ca6c76758/nihms-1939035-f0007.jpg

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