Enhanced transcriptional heterogeneity mediated by NF-κB super-enhancers

The transcription factor NF-κB, which plays an important role in cell fate determination, is involved in the activation of super-enhancers (SEs). However, the biological functions of the NF-κB SEs in gene control are not fully elucidated. We investigated the characteristics of NF-κB-mediated SE acti...

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Veröffentlicht in:PLoS genetics 2022-06, Vol.18 (6), p.e1010235-e1010235
Hauptverfasser: Wibisana, Johannes N, Inaba, Takehiko, Shinohara, Hisaaki, Yumoto, Noriko, Hayashi, Tetsutaro, Umeda, Mana, Ebisawa, Masashi, Nikaido, Itoshi, Sako, Yasushi, Okada, Mariko
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Sprache:eng
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Zusammenfassung:The transcription factor NF-κB, which plays an important role in cell fate determination, is involved in the activation of super-enhancers (SEs). However, the biological functions of the NF-κB SEs in gene control are not fully elucidated. We investigated the characteristics of NF-κB-mediated SE activity using fluorescence imaging of RelA, single-cell transcriptome and chromatin accessibility analyses in anti-IgM-stimulated B cells. The formation of cell stimulation-induced nuclear RelA foci was abolished in the presence of hexanediol, suggesting an underlying process of liquid-liquid phase separation. The gained SEs induced a switch-like expression and enhanced cell-to-cell variability in transcriptional response. These properties were correlated with the number of gained cis-regulatory interactions, while switch-like gene induction was associated with the number of NF-κB binding sites in SE. Our study suggests that NF-κB SEs have an important role in the transcriptional regulation of B cells possibly through liquid condensate formation consisting of macromolecular interactions.
ISSN:1553-7404
1553-7390
1553-7404
DOI:10.1371/journal.pgen.1010235