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YTHDF1 facilitates PRC1-mediated H2AK119ub in human ES cells
Jingyuan Zhang1,2,3,4,5,6, Tianyu Wang1,2,3,4,5, Ruona Shi2,3
1CAS Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
YTHDF1, an RNA-binding protein, is newly found in the nucleus of human embryonic stem cells, where it interacts with PRC1 to regulate gene expression and neural development.
Area of Science:
- Epigenetics
- Molecular Biology
- Developmental Biology
Background:
- Polycomb repressive complexes (PRCs) are crucial for cell fate decisions and are implicated in diseases.
- PRCs mediate histone modifications like H3K27me3 and H2AK119ub.
- Mechanisms of PRC recruitment to chromatin are not fully understood.
Purpose of the Study:
- To investigate the role of YTHDF1 in Polycomb repressive complex 1 (PRC1) function.
- To explore the noncanonical nuclear functions of YTHDF1 in human embryonic stem cells (hESCs).
Main Methods:
- Co-immunoprecipitation to assess protein interactions.
- Chromatin immunoprecipitation to identify gene targets.
- RNA interference (RNAi) for gene knockdown.
- Immunofluorescence to determine protein localization.
Main Results:
- YTHDF1, typically cytoplasmic, was found to localize in the nucleus of hESCs.
- Nuclear YTHDF1 associates with RNF2, a PRC1 component, and H2AK119ub.
- YTHDF1 knockdown reduced H2AK119ub levels and promoted neural differentiation.
Conclusions:
- YTHDF1 plays a noncanonical role in PRC1-mediated gene regulation within the nucleus.
- YTHDF1 influences H2AK119ub modification and neural differentiation in hESCs.
- This study reveals a novel mechanism linking RNA binding proteins to epigenetic regulation.
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