Evidence map›Paper›PMID 41882225›Full record

ArticleThe EMBO journal2026

FGF4 initiates X-chromosome inactivation via activating YY1 and prompting loss of pluripotency factors.

Lizhu Ma, Wei Fu, Lei An, Qianying Yang, Ruiqi Hai, Guangyin Xi, Yinjuan Wang, Juan Liu, Chao Zhang, Yao Fu and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The EMBO journal, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Lizhu Ma *Frontiers Science Center for Molecular Design Breeding (MOE), State Key Laboratory of Animal Biotech Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture and Rural Afairs, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, People's Republic of China.
Wei Fu *Frontiers Science Center for Molecular Design Breeding (MOE), State Key Laboratory of Animal Biotech Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture and Rural Afairs, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, People's Republic of China.
Lei An *Frontiers Science Center for Molecular Design Breeding (MOE), State Key Laboratory of Animal Biotech Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture and Rural Afairs, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, People's Republic of China.
Qianying YangFrontiers Science Center for Molecular Design Breeding (MOE), State Key Laboratory of Animal Biotech Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture and Rural Afairs, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, People's Republic of China.
Ruiqi HaiFrontiers Science Center for Molecular Design Breeding (MOE), State Key Laboratory of Animal Biotech Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture and Rural Afairs, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, People's Republic of China.ORCID http://orcid.org/0009-0003-5237-8304
Guangyin XiFrontiers Science Center for Molecular Design Breeding (MOE), State Key Laboratory of Animal Biotech Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture and Rural Afairs, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, People's Republic of China.
Yinjuan WangFrontiers Science Center for Molecular Design Breeding (MOE), State Key Laboratory of Animal Biotech Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture and Rural Afairs, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, People's Republic of China.
Juan LiuFrontiers Science Center for Molecular Design Breeding (MOE), State Key Laboratory of Animal Biotech Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture and Rural Afairs, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, People's Republic of China.
Chao ZhangFrontiers Science Center for Molecular Design Breeding (MOE), State Key Laboratory of Animal Biotech Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture and Rural Afairs, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, People's Republic of China.
Yao FuFrontiers Science Center for Molecular Design Breeding (MOE), State Key Laboratory of Animal Biotech Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture and Rural Afairs, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, People's Republic of China.
Zhenni ZhangFrontiers Science Center for Molecular Design Breeding (MOE), State Key Laboratory of Animal Biotech Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture and Rural Afairs, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, People's Republic of China.
Xiaodong WangFrontiers Science Center for Molecular Design Breeding (MOE), State Key Laboratory of Animal Biotech Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture and Rural Afairs, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, People's Republic of China.
Jianhui TianFrontiers Science Center for Molecular Design Breeding (MOE), State Key Laboratory of Animal Biotech Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture and Rural Afairs, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, People's Republic of China. tianjh@cau.edu.cn.ORCID http://orcid.org/0000-0003-4509-6336

Funding

MOST | National Key Research and Development Program of China (NKPs) 2023YFD1300504
6 · The paper itself

Abstract

X-chromosome inactivation (XCI) balances gene expression between sexes in mammals and is essential to female development. XCI initiation strictly relies on the upregulation of long noncoding RNA Xist upon differentiation. Despite the co-occurrence and tight correlation between XCI and differentiation, master coordinators to synchronize XCI and differentiation remain ill-defined. Here, we report that FGF4, an autocrine differentiation-prompting stimulus, is essential for Xist upregulation and XCI initiation in mouse embryonic stem cells (ESCs). Either Fgf4 deficiency or FGFR blocking results in failure of Xist upregulation and XCI initiation. Mechanistically, FGF4 initiates XCI in a MEK/ERK-dependent manner, via two parallel but opposing pathways: i)FGF4 phosphorylates and activates YY1, a robust transcription activator of Xist, and ii) FGF4 facilitates decline of pluripotency factors Prdm14, Nanog and Rex1, resolving Xist repression. Together, we show how FGF4 comprehensively orchestrates XCI and ESC differentiation, and ensures XCI initiation by coordinating two opposing regulators that directly influence Xist transcription. The FGF-ERK-YY1 axis also constitutes  a missing link between ubiquitously expressed Yy1 and its functional activation responsible for Xist upregulation and XCI initiation.

Indexed as

Fibroblast Growth Factor 4X Chromosome InactivationYY1 Transcription FactorAnimalsCell DifferentiationFemaleMAP Kinase Signaling SystemMiceMouse Embryonic Stem CellsRNA, Long NoncodingFgf4 protein, mouseFibroblast Growth Factor 4RNA, Long NoncodingXIST non-coding RNAYy1 protein, mouseYY1 Transcription FactorEmbryonic Stem CellsFGF4MEK/ERKX-chromosome InactivationYY1

Identifiers

PMID41882225
PMCPMC13144533

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.