1. Chromatin-associated YTHDC1 coordinates heat-induced reprogramming of gene expression.
- Author
-
Timcheva K, Dufour S, Touat-Todeschini L, Burnard C, Carpentier MC, Chuffart F, Merret R, Helsmoortel M, Ferré S, Grézy A, Couté Y, Rousseaux S, Khochbin S, Vourc'h C, Bousquet-Antonelli C, Kiernan R, Seigneurin-Berny D, and Verdel A
- Subjects
- Humans, Heat-Shock Proteins metabolism, Gene Expression, RNA Splicing Factors metabolism, Nerve Tissue Proteins metabolism, Chromatin, Heat-Shock Response genetics
- Abstract
Heat stress (HS) induces a cellular response leading to profound changes in gene expression. Here, we show that human YTHDC1, a reader of N
6 -methyladenosine (m6 A) RNA modification, mostly associates to the chromatin fraction and that HS induces a redistribution of YTHDC1 across the genome, including to heat-induced heat shock protein (HSP) genes. YTHDC1 binding to m6 A-modified HSP transcripts co-transcriptionally promotes expression of HSPs. In parallel, hundreds of the genes enriched in YTHDC1 during HS have their transcripts undergoing YTHDC1- and m6 A-dependent intron retention. Later, YTHDC1 concentrates within nuclear stress bodies (nSBs) where it binds to m6 A-modified SATIII non-coding RNAs, produced in an HSF1-dependent manner upon HS. These findings reveal that YTHDC1 plays a central role in a chromatin-associated m6 A-based reprogramming of gene expression during HS. Furthermore, they support the model where the subsequent and temporary sequestration of YTHDC1 within nSBs calibrates the timing of this YTHDC1-dependent gene expression reprogramming., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2022
- Full Text
- View/download PDF