Faculty, Staff and Student Publications
Publication Date
11-1-2022
Journal
Cell Reports
Abstract
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.
Keywords
3D genome organization, CP: Molecular biology, Cut&Run, PRO-seq, Hi-C, HiChIP, dCas9 tethering, enhancers, nuclear pore complex, nucleoporins, transcription
DOI
10.1016/j.celrep.2022.111576
PMID
36323253
PMCID
PMC9744245
PubMedCentral® Posted Date
December 2022
PubMedCentral® Full Text Version
Author MSS
Published Open-Access
yes