Ligand-dependent enhancer activation indirectly modulates non-target promoters in a chromatin domain.

Authors

Darshika Bohra, Zubairul Islam, Sundarraj Nidharshan, Aprotim Mazumder, Dimple Notani

Published in

eLife. Volume 13. Jul 07, 2026. Epub Jul 07, 2026.

Abstract

Transcription activation of genes by estrogen is driven by enhancers, which are often located within the same topologically associating domain (TAD) as non-targeted promoters. We investigated how acute enhancer-driven activation affects neighbouring non-target genes within the same TAD. Using single-molecule RNA FISH (smFISH), we tracked the transcription of TFF1 (enhancer-target gene) and TFF3 (non-target gene) during estrogen stimulation. We observed mutually exclusive expression patterns: TFF1 expression peaked at 1 hr, while TFF3 reached its peak at 3 hr after TFF1 activation had diminished. Chromatin looping data indicated that the enhancer loops with the TFF1 gene but not TFF3, suggesting that TFF3 upregulation is not due to direct enhancer-promoter interactions. CRISPR deletion of the enhancer affected TFF1 transcription more acutely than TFF3. 1,6-hexanediol (HD) exposure suggested that the TFF1 enhancer:promoter undergoes a potential ERα-mediated condensate formation, which sequesters the transcriptional machinery and inhibits TFF3 expression. As estrogen signaling fades at 3 hr, TFF1 expression declines while TFF3 expression increases. Our findings reveal that enhancer-driven activation can indirectly repress neighboring genes within the same TAD, highlighting a dynamic shift in gene expression as signaling progresses.

PMID:
42412908
Bibliographic data and abstract were imported from PubMed on 08 Jul 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.