Acute depletion of human core nucleoporin reveals direct roles in transcription control but dispensability for 3D genome organization
The nuclear pore complex (NPC) comprises more than 30 nucleoporins (NUPs) and is a hallmark of eukaryotes. NUPs have been suggested to be important in regulating gene transcription and 3D genome organization. However, evidence in support of their direct roles remains limited. Here, by Cut&Run, w...
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Published in | Cell reports (Cambridge) Vol. 41; no. 5; p. 111576 |
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Main Authors | , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
01.11.2022
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Subjects | |
Online Access | Get full text |
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Summary: | The nuclear pore complex (NPC) comprises more than 30 nucleoporins (NUPs) and is a hallmark of eukaryotes. NUPs have been suggested to be important in regulating gene transcription and 3D genome organization. However, evidence in support of their direct roles remains limited. Here, by Cut&Run, we find that core NUPs display broad but also cell-type-specific association with active promoters and enhancers in human cells. Auxin-mediated rapid depletion of two NUPs demonstrates that NUP93, but not NUP35, directly and specifically controls gene transcription. NUP93 directly activates genes with high levels of RNA polymerase II loading and transcriptional elongation by facilitating full BRD4 recruitment to their active enhancers. dCas9-based tethering confirms a direct and causal role of NUP93 in gene transcriptional activation. Unexpectedly, in situ Hi-C and H3K27ac or H3K4me1 HiChIP results upon acute NUP93 depletion show negligible changesS2211-1247(22)01437-1 of 3D genome organization ranging from A/B compartments and topologically associating domains (TADs) to enhancer-promoter contacts. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 AUTHOR CONTRIBUTIONS W.L. and X.Z. conceived the project. In the wet lab, X.Z., R.W., and W.L. performed most of the experiments with help from J.-H.L., F.X., L.B., P.T.N., G.L., J.K., and S.-P.K. In the dry lab, C.Q. and R.W. performed all analyses with help from J.S., L.M.S., and L.H. T.I.M. helped with N-SIM imaging. W.L., X.Z., and C.Q. wrote the manuscript. All authors contributed to commenting on and editing the manuscript. |
ISSN: | 2211-1247 2211-1247 |
DOI: | 10.1016/j.celrep.2022.111576 |