RT Journal Article
SR Electronic
T1 Imaging and single cell sequencing analyses of super-enhancer activation mediated by NF-κB in B cells
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.07.13.452147
DO 10.1101/2021.07.13.452147
A1 Johannes N. Wibisana
A1 Takehiko Inaba
A1 Hisaaki Shinohara
A1 Noriko Yumoto
A1 Tetsutaro Hayashi
A1 Mana Umeda
A1 Masashi Ebisawa
A1 Itoshi Nikaido
A1 Yasushi Sako
A1 Mariko Okada
YR 2021
UL http://biorxiv.org/content/early/2021/07/13/2021.07.13.452147.abstract
AB The NF-κB signaling pathway, which plays an important role in cell fate determination in various cells, has been found to be involved in the activation of long clusters of enhancers known as super-enhancers (SEs) for transcriptional regulation. However, the contribution of NF-κB to SEs has not yet been validated under microscopic observation. Using fluorescence imaging, single-cell transcriptome, and chromatin accessibility analyses, we show that NF-κB subunit RelA nuclear foci formation and single-cell gene expression demonstrate SE-like properties in anti-IgM-stimulated B cells. This contributed to bimodal and enhanced cell-to-cell variability in transcriptional response. Furthermore, we found that the predicted cis-regulatory interacting genomic regions from chromatin co-accessibility analysis were associated with the observed transcriptional heterogeneity. These findings suggest that NF-κB-mediated SE formation is important for the expression of NF-κB target genes and the amplification of transcriptional heterogeneity in response to environmental stimuli in B cells.Competing Interest StatementThe authors have declared no competing interest.