---
OA_place: publisher
OA_type: hybrid
PlanS_conform: '1'
_id: '19602'
abstract:
- lang: eng
text: N4-methylcytosine (4mC) is an important DNA modification in prokaryotes, but
its relevance and even its presence in eukaryotes have been mysterious. Here we
show that spermatogenesis in the liverwort Marchantia polymorpha involves two
waves of extensive DNA methylation reprogramming. First, 5-methylcytosine (5mC)
expands from transposons to the entire genome. Notably, the second wave installs
4mC throughout genic regions, covering over 50% of CG sites in sperm. 4mC requires
a methyltransferase (MpDN4MT1a) that is specifically expressed during late spermiogenesis.
Deletion of MpDN4MT1a alters the sperm transcriptome, causes sperm swimming and
fertility defects, and impairs post-fertilization development. Our results reveal
extensive 4mC in a eukaryote, identify a family of eukaryotic methyltransferases,
and elucidate the biological functions of 4mC in reproductive development, thereby
expanding the repertoire of functional eukaryotic DNA modifications.
acknowledged_ssus:
- _id: Bio
- _id: ScienComp
acknowledgement: We thank Sir Richard Roberts (NEB) for the kind gift of anti-4mC
antibodies. We are also grateful to the JIC Small Molecule Mass Spectrometry (Lionel
Hill) and Chemistry (Martin Rejzek) platforms as well as the High Resolution Metabolomics
Laboratory (Manfred Beckmann, Aberystwyth University) for their assistance with
LC-MS. Additionally, we acknowledge the assistance of the JIC Bioimaging Facility
and ISTA Imaging and Optics Facility for microscopy. Finally, we appreciate the
High Performance Computing resources provided by the ISTA Scientific Computing Facility
and Norwich BioScience Institute Partnership Computing Infrastructure. This work
was funded by a Sainsbury Charitable Foundation studentship (J.W.), a UKRI-BBSRC
Doctoral Training Partnerships studentship (BBT0087171 to J.T.), a European Research
Council Starting Grant (“SexMeth” 804981 to J.W., S.X., and X.F.), two Biotechnology
and Biological Sciences Research Council (BBSRC) grants (BBS0096201 and BBP0135111
to J.Z., M.V., and X.F.), an EMBO Long Term Fellowship (Y.L.), an ISTA Bridge Fellowship
(S.X.), and ISTA core funding (Y.Y. and X.F.).
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: James
full_name: Walker, James
last_name: Walker
- first_name: Jingyi
full_name: Zhang, Jingyi
last_name: Zhang
- first_name: Yalin
full_name: Liu, Yalin
last_name: Liu
- first_name: Shujuan
full_name: Xu, Shujuan
id: 9724dd9d-f591-11ee-bd51-e97ed0652286
last_name: Xu
- first_name: Yiming
full_name: Yu, Yiming
id: 318e643b-8b61-11ed-b69e-aafa103ec8dd
last_name: Yu
orcid: 0000-0002-9919-7282
- first_name: Martin
full_name: Vickers, Martin
last_name: Vickers
- first_name: Weizhi
full_name: Ouyang, Weizhi
id: fec73395-8b60-11ed-b69e-927fda99c743
last_name: Ouyang
- first_name: Judit
full_name: Tálas, Judit
last_name: Tálas
- first_name: Liam
full_name: Dolan, Liam
last_name: Dolan
- first_name: Keiji
full_name: Nakajima, Keiji
last_name: Nakajima
- first_name: Xiaoqi
full_name: Feng, Xiaoqi
id: e0164712-22ee-11ed-b12a-d80fcdf35958
last_name: Feng
orcid: 0000-0002-4008-1234
citation:
ama: Walker J, Zhang J, Liu Y, et al. Extensive N4 cytosine methylation is essential
for Marchantia sperm function. Cell. 2025;188(11):2890-2906.e14. doi:10.1016/j.cell.2025.03.014
apa: Walker, J., Zhang, J., Liu, Y., Xu, S., Yu, Y., Vickers, M., … Feng, X. (2025).
Extensive N4 cytosine methylation is essential for Marchantia sperm function.
Cell. Elsevier. https://doi.org/10.1016/j.cell.2025.03.014
chicago: Walker, James, Jingyi Zhang, Yalin Liu, Shujuan Xu, Yiming Yu, Martin Vickers,
Weizhi Ouyang, et al. “Extensive N4 Cytosine Methylation Is Essential for Marchantia
Sperm Function.” Cell. Elsevier, 2025. https://doi.org/10.1016/j.cell.2025.03.014.
ieee: J. Walker et al., “Extensive N4 cytosine methylation is essential for
Marchantia sperm function,” Cell, vol. 188, no. 11. Elsevier, p. 2890–2906.e14,
2025.
ista: Walker J, Zhang J, Liu Y, Xu S, Yu Y, Vickers M, Ouyang W, Tálas J, Dolan
L, Nakajima K, Feng X. 2025. Extensive N4 cytosine methylation is essential for
Marchantia sperm function. Cell. 188(11), 2890–2906.e14.
mla: Walker, James, et al. “Extensive N4 Cytosine Methylation Is Essential for Marchantia
Sperm Function.” Cell, vol. 188, no. 11, Elsevier, 2025, p. 2890–2906.e14,
doi:10.1016/j.cell.2025.03.014.
short: J. Walker, J. Zhang, Y. Liu, S. Xu, Y. Yu, M. Vickers, W. Ouyang, J. Tálas,
L. Dolan, K. Nakajima, X. Feng, Cell 188 (2025) 2890–2906.e14.
corr_author: '1'
date_created: 2025-04-20T22:01:28Z
date_published: 2025-05-29T00:00:00Z
date_updated: 2025-12-29T13:41:13Z
day: '29'
ddc:
- '570'
department:
- _id: XiFe
doi: 10.1016/j.cell.2025.03.014
ec_funded: 1
external_id:
isi:
- '001504744800006'
pmid:
- '40209706'
file:
- access_level: open_access
checksum: 0dcc2feb368dfe7c4890093366b2dacb
content_type: application/pdf
creator: dernst
date_created: 2025-12-29T13:40:32Z
date_updated: 2025-12-29T13:40:32Z
file_id: '20871'
file_name: 2025_Cell_Walker.pdf
file_size: 11622960
relation: main_file
success: 1
file_date_updated: 2025-12-29T13:40:32Z
has_accepted_license: '1'
intvolume: ' 188'
isi: 1
issue: '11'
language:
- iso: eng
month: '05'
oa: 1
oa_version: Published Version
page: 2890-2906.e14
pmid: 1
project:
- _id: bdb51a6e-d553-11ed-ba76-c2025f3d5725
call_identifier: H2020
grant_number: '804981'
name: Establishment, modulation and inheritance of sexual lineage specific DNA methylation
in plants
publication: Cell
publication_identifier:
eissn:
- 1097-4172
issn:
- 0092-8674
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: Extensive N4 cytosine methylation is essential for Marchantia sperm function
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 188
year: '2025'
...