RNA fine-tunes estrogen receptor-alpha binding on low-affinity DNA motifs for transcriptional regulation.

Chromatin DNA-motifs Estrogen Receptor-Alpha Non-Coding RNA Transcription Factors

Journal

The EMBO journal
ISSN: 1460-2075
Titre abrégé: EMBO J
Pays: England
ID NLM: 8208664

Informations de publication

Date de publication:
16 Sep 2024
Historique:
received: 29 08 2023
accepted: 15 07 2024
revised: 12 06 2024
medline: 17 9 2024
pubmed: 17 9 2024
entrez: 16 9 2024
Statut: aheadofprint

Résumé

Transcription factors (TFs) regulate gene expression by binding with varying strengths to DNA via their DNA-binding domain. Additionally, some TFs also interact with RNA, which modulates transcription factor binding to chromatin. However, whether RNA-mediated TF binding results in differential transcriptional outcomes remains unknown. In this study, we demonstrate that estrogen receptor α (ERα), a ligand-activated TF, interacts with RNA in a ligand-dependent manner. Defects in RNA binding lead to genome-wide loss of ERα recruitment, particularly at weaker ERα-motifs. Furthermore, ERα mobility in the nucleus increases in the absence of its RNA-binding capacity. Unexpectedly, this increased mobility coincides with robust polymerase loading and transcription of ERα-regulated genes that harbor low-strength motifs. However, highly stable binding of ERα on chromatin negatively impacts ligand-dependent transcription. Collectively, our results suggest that RNA interactions spatially confine ERα on low-affinity sites to fine-tune gene transcription.

Identifiants

pubmed: 39284910
doi: 10.1038/s44318-024-00225-y
pii: 10.1038/s44318-024-00225-y
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : Wellcome Trust DBT India Alliance (India Alliance)
ID : IA/S/23/1/506749
Organisme : Department of Science and Technology, Ministry of Science and Technology, India (DST)
ID : CRG/2019/005714
Organisme : European Molecular Biology Organization (EMBO)
ID : GIN
Organisme : TIFR | National Centre for Biological Sciences (NCBS)
ID : RTI 4006

Informations de copyright

© 2024. The Author(s).

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Auteurs

Deepanshu Soota (D)

National Center for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, Karnataka, 560065, India.

Bharath Saravanan (B)

National Center for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, Karnataka, 560065, India.
SASTRA Deemed University, Thanjavur, Tamil Nadu, 613401, India.

Rajat Mann (R)

National Center for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, Karnataka, 560065, India.

Tripti Kharbanda (T)

National Center for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, Karnataka, 560065, India.

Dimple Notani (D)

National Center for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, Karnataka, 560065, India. dnotani@ncbs.res.in.

Classifications MeSH