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

Autor:	Soota D; National Center for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, Karnataka, 560065, India., Saravanan B; National Center for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, Karnataka, 560065, India.; SASTRA Deemed University, Thanjavur, Tamil Nadu, 613401, India., Mann R; National Center for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, Karnataka, 560065, India., Kharbanda T; National Center for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, Karnataka, 560065, India., Notani D; National Center for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, Karnataka, 560065, India. dnotani@ncbs.res.in.
Jazyk:	angličtina
Zdroj:	The EMBO journal [EMBO J] 2024 Nov; Vol. 43 (21), pp. 5186-5210. Date of Electronic Publication: 2024 Sep 16.
DOI:	10.1038/s44318-024-00225-y
Abstrakt:	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. (© 2024. The Author(s).)
Databáze:	MEDLINE
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