Functional role of Tet-mediated RNA hydroxymethylcytosine in mouse ES cells and during differentiation

Functional role of Tet-mediated RNA hydroxymethylcytosine in mouse ES cells and during differentiation.

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Item Type: Article
Status: Published
Official URL: https://doi.org/10.1038/s41467-020-18729-6
Journal or Publication Title: Nature Communications
Volume: 11
Number: 1
Date: 2020
Divisions: Epigenetics and RNA Biology
Depositing User: General Admin
Identification Number: 10.1038/s41467-020-18729-6
ISSN: 2041-1723
Date Deposited: 04 Jan 2021 03:06
Abstract:

Tet-enzyme-mediated 5-hydroxymethylation of cytosines in DNA plays a crucial role in mouse embryonic stem cells (ESCs). In RNA also, 5-hydroxymethylcytosine (5hmC) has recently been evidenced, but its physiological roles are still largely unknown. Here we show the contribution and function of this mark in mouse ESCs and differentiating embryoid bodies. Transcriptome-wide mapping in ESCs reveals hundreds of messenger RNAs marked by 5hmC at sites characterized by a defined unique consensus sequence and particular features. During differentiation a large number of transcripts, including many encoding key pluripotency-related factors (such as Eed and Jarid2), show decreased cytosine hydroxymethylation. Using Tet-knockout ESCs, we find Tet enzymes to be partly responsible for deposition of 5hmC in mRNA. A transcriptome-wide search further reveals mRNA targets to which Tet1 and Tet2 bind, at sites showing a topology similar to that of 5hmC sites. Tet-mediated RNA hydroxymethylation is found to reduce the stability of crucial pluripotency-promoting transcripts. We propose that RNA cytosine 5-hydroxymethylation by Tets is a mark of transcriptome flexibility, inextricably linked to the balance between pluripotency and lineage commitment.

Creators:
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Lan, Jie
UNSPECIFIED
Rajan, Nicholas
UNSPECIFIED
Bizet, Martin
UNSPECIFIED
Penning, Audrey
UNSPECIFIED
Singh, Nitesh K.
UNSPECIFIED
Guallar, Diana
UNSPECIFIED
Calonne, Emilie
UNSPECIFIED
Li Greci, Andrea
UNSPECIFIED
Bonvin, Elise
UNSPECIFIED
Deplus, Rachel
UNSPECIFIED
Hsu, Phillip J.
UNSPECIFIED
Nachtergaele, Sigrid
UNSPECIFIED
Ma, Chengjie
UNSPECIFIED
Song, Renhua
UNSPECIFIED
Fuentes-Iglesias, Alejandro
UNSPECIFIED
Hassabi, Bouchra
UNSPECIFIED
Putmans, Pascale
UNSPECIFIED
Mies, Frédérique
UNSPECIFIED
Menschaert, Gerben
UNSPECIFIED
Wong, Justin J. L.
UNSPECIFIED
Wang, Jianlong
UNSPECIFIED
Fidalgo, Miguel
UNSPECIFIED
Yuan, Bifeng
UNSPECIFIED
Fuks, François
UNSPECIFIED
Last Modified: 04 Jan 2021 03:06
URI: https://eprints.centenary.org.au/id/eprint/756

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