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核篮蛋白Mlp1和Nup2驱动热休克诱导的三维基因组重组。

Nuclear basket proteins Mlp1 and Nup2 drive heat shock-induced 3D genome restructuring.

作者信息

Mohajan Suman, Rubio Linda S, Gross David S

机构信息

Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA 71130.

出版信息

bioRxiv. 2025 Jan 2:2025.01.01.631024. doi: 10.1101/2025.01.01.631024.

DOI:10.1101/2025.01.01.631024
PMID:39803495
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11722380/
Abstract

The nuclear pore complex (NPC), a multisubunit complex located within the nuclear envelope, regulates RNA export and the import and export of proteins. Here we address the role of the NPC in driving thermal stress-induced 3D genome repositioning of () genes in yeast. We found that two nuclear basket proteins, Mlp1 and Nup2, although dispensable for NPC integrity, are required for driving genes into coalesced chromatin clusters, consistent with their strong, heat shock-dependent recruitment to gene regulatory and coding regions. gene clustering occurs predominantly within the nucleoplasm and is independent of the essential scaffold-associated proteins Nup1 and Nup145. Notably, double depletion of Mlp1 and Nup2 has little effect on the formation of Heat Shock Factor 1 (Hsf1)-containing transcriptional condensates, Hsf1 and Pol II recruitment to genes, or mRNA abundance. Our results define a 3D genome restructuring role for nuclear basket proteins extrinsic to the NPC and downstream of gene activation.

摘要

核孔复合体(NPC)是位于核膜内的多亚基复合体,负责调节RNA输出以及蛋白质的输入和输出。在此,我们探讨了NPC在驱动酵母中热应激诱导的()基因三维基因组重定位中的作用。我们发现,两种核篮蛋白Mlp1和Nup2,虽然对于NPC的完整性并非必需,但对于将基因驱动到凝聚的染色质簇中却是必需的,这与它们在热休克依赖下被强力招募到基因调控区和编码区一致。基因聚类主要发生在核质内,且独立于必需的支架相关蛋白Nup1和Nup145。值得注意的是,Mlp1和Nup2的双重缺失对含热休克因子1(Hsf1)的转录凝聚物的形成、Hsf1和Pol II募集到基因上,或mRNA丰度几乎没有影响。我们的结果确定了核篮蛋白在NPC外部且在基因激活下游的三维基因组重组作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12b6/11722380/c47fd1a2f8a0/nihpp-2025.01.01.631024v1-f0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12b6/11722380/74f37156461c/nihpp-2025.01.01.631024v1-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12b6/11722380/95fd1c10393b/nihpp-2025.01.01.631024v1-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12b6/11722380/480323e6b84b/nihpp-2025.01.01.631024v1-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12b6/11722380/e21b02cc2e81/nihpp-2025.01.01.631024v1-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12b6/11722380/a8f0488bee19/nihpp-2025.01.01.631024v1-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12b6/11722380/52c5a3a7a20d/nihpp-2025.01.01.631024v1-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12b6/11722380/307cc02cc01c/nihpp-2025.01.01.631024v1-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12b6/11722380/9b73d9193b61/nihpp-2025.01.01.631024v1-f0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12b6/11722380/c47fd1a2f8a0/nihpp-2025.01.01.631024v1-f0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12b6/11722380/74f37156461c/nihpp-2025.01.01.631024v1-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12b6/11722380/95fd1c10393b/nihpp-2025.01.01.631024v1-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12b6/11722380/480323e6b84b/nihpp-2025.01.01.631024v1-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12b6/11722380/e21b02cc2e81/nihpp-2025.01.01.631024v1-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12b6/11722380/a8f0488bee19/nihpp-2025.01.01.631024v1-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12b6/11722380/52c5a3a7a20d/nihpp-2025.01.01.631024v1-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12b6/11722380/307cc02cc01c/nihpp-2025.01.01.631024v1-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12b6/11722380/9b73d9193b61/nihpp-2025.01.01.631024v1-f0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12b6/11722380/c47fd1a2f8a0/nihpp-2025.01.01.631024v1-f0009.jpg

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本文引用的文献

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Mol Cell. 2025 Mar 20;85(6):1101-1116.e8. doi: 10.1016/j.molcel.2025.02.013. Epub 2025 Mar 10.
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Heat Shock Factor 1 forms nuclear condensates and restructures the yeast genome before activating target genes.热休克因子 1 在激活靶基因之前形成核凝聚体并重构酵母基因组。
Elife. 2024 Oct 15;12:RP92464. doi: 10.7554/eLife.92464.
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Transcription factor condensates, 3D clustering, and gene expression enhancement of the regulon.
转录因子凝聚物、3D 聚类和调控基因表达增强。
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Nuclear basket proteins regulate the distribution and mobility of nuclear pore complexes in budding yeast.核篮蛋白调节出芽酵母中核孔复合体的分布和流动性。
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DNA methylation-based high-resolution mapping of long-distance chromosomal interactions in nucleosome-depleted regions.基于 DNA 甲基化的核小体缺失区域中长距离染色体相互作用的高分辨率图谱绘制。
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Transcriptional condensates and phase separation: condensing information across scales and mechanisms.转录凝聚物和相分离:跨尺度和机制凝聚信息。
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