Autophagy receptor NDP52 alters DNA conformation to modulate RNA polymerase II transcription.
Autophagy receptor NDP52 alters DNA conformation to modulate RNA polymerase II transcription.
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DOI：
10.1038/s41467-023-38572-9
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发表时间：
2023-05-18
影响因子：
16.6
通讯作者：
Toseland, Christopher P.
中科院分区：
文献类型：
--
作者：
dos Santos, Alia;Rollins, Daniel E.;Hari-Gupta, Yukti;McArthur, Hannah;Du, Mingxue;Ru, Sabrina Yong Zi;Pidlisna, Kseniia;Stranger, Ane;Lorgat, Faeeza;Lambert, Danielle;Brown, Ian;Howland, Kevin;Aaron, Jesse;Wang, Lin;Ellis, Peter J. I.;Chew, Teng-Leong;Martin-Fernandez, Marisa;Pyne, Alice L. B.;Toseland, Christopher P.
NDP52是一种自噬受体，参与识别和降解入侵的病原体和受损的细胞器。虽然NDP52最先在细胞核中被发现，并在整个细胞中表达，但到目前为止，NDP52的核功能尚不清楚。在这里，我们使用多学科的方法来表征NDP52的生化特性和核角色。我们发现NDP52与RNA聚合酶II(RNAPII)在转录起始点上形成簇，并且它的过表达促进了额外的转录簇的形成。我们还表明，NDP52的缺失影响了两个模型哺乳动物细胞中的整体基因表达水平，而转录抑制影响了NDP52在细胞核中的空间组织和分子动力学。这直接将NDP52与RNAPII依赖的转录中的一个角色联系起来。此外，我们还发现NDP52与双链DNA(DsDNA)具有高亲和力和特异性结合，这种相互作用在体外会导致DNA结构的变化。这一点，加上我们的蛋白质组学数据表明，与核小体重塑蛋白和DNA结构调节器的相互作用丰富，表明NDP52在染色质调节中可能具有功能。总体而言，我们在这里揭示了NDP52在基因表达和DNA结构调控中的核作用。自噬受体NDP52被招募到细胞核，在那里它可以结合DNA。作者表明，这促进了染色质可及性的变化，染色质可及性支持转录启动，在自噬和转录调控之间提供了直接联系。
NDP52 is an autophagy receptor involved in the recognition and degradation of invading pathogens and damaged organelles. Although NDP52 was first identified in the nucleus and is expressed throughout the cell, to date, there is no clear nuclear functions for NDP52. Here, we use a multidisciplinary approach to characterise the biochemical properties and nuclear roles of NDP52. We find that NDP52 clusters with RNA Polymerase II (RNAPII) at transcription initiation sites and that its overexpression promotes the formation of additional transcriptional clusters. We also show that depletion of NDP52 impacts overall gene expression levels in two model mammalian cells, and that transcription inhibition affects the spatial organisation and molecular dynamics of NDP52 in the nucleus. This directly links NDP52 to a role in RNAPII-dependent transcription. Furthermore, we also show that NDP52 binds specifically and with high affinity to double-stranded DNA (dsDNA) and that this interaction leads to changes in DNA structure in vitro. This, together with our proteomics data indicating enrichment for interactions with nucleosome remodelling proteins and DNA structure regulators, suggests a possible function for NDP52 in chromatin regulation. Overall, here we uncover nuclear roles for NDP52 in gene expression and DNA structure regulation. An autophagy receptor, NDP52, is recruited to the nucleus where it can bind DNA. The authors show this promotes changes in chromatin accessibility which supports transcription initiation, providing a direct link between autophagy and transcription regulation.
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影响因子：
48
作者：
Abrahamsson, Sara;Chen, Jiji;Hajj, Bassam;Stallinga, Sjoerd;Katsov, Alexander Y.;Wisniewski, Jan;Mizuguchi, Gaku;Soule, Pierre;Mueller, Florian;Darzacq, Claire Dugast;Darzacq, Xavier;Wu, Carl;Bargmann, Cornelia I.;Agard, David A.;Dahan, Maxime;Gustafsson, Mats G. L.
通讯作者：
Gustafsson, Mats G. L.
影响因子：
4.6
作者：
Cho WK;Jayanth N;Mullen S;Tan TH;Jung YJ;Cissé II
通讯作者：
Cissé II
影响因子：
7.5
作者：
Cremer, Thomas;Cremer, Marion;Fakan, Stanislav
通讯作者：
Fakan, Stanislav
影响因子：
7.7
作者：
Cho, Won-Ki;Jayanth, Namrata;Cisse, Ibrahim I.
通讯作者：
Cisse, Ibrahim I.
DOI：
10.1016/j.ymeth.2021.01.008
发表时间：
2021-09
期刊：
Methods (San Diego, Calif.)
影响因子：
--
作者：
Beton JG;Moorehead R;Helfmann L;Gray R;Hoogenboom BW;Joseph AP;Topf M;Pyne ALB
通讯作者：
Pyne ALB