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Zfp281 is essential for mouse epiblast maturation through transcriptional and epigenetic control of Nodal signaling.

eLife | Nov 23, 2017

Pluripotency is defined by a cell's potential to differentiate into any somatic cell type. How pluripotency is transited during embryo implantation, followed by cell lineage specification and establishment of the basic body plan, is poorly understood. Here we report the transcription factor Zfp281 functions in the exit from naive pluripotency occurring coincident with pre-to-post-implantation mouse embryonic development. By characterizing Zfp281 mutant phenotypes and identifying Zfp281 gene targets and protein partners in developing embryos and cultured pluripotent stem cells, we establish critical roles for Zfp281 in activating components of the Nodal signaling pathway and lineage-specific genes. Mechanistically, Zfp281 cooperates with histone acetylation and methylation complexes at target gene enhancers and promoters to exert transcriptional activation and repression, as well as epigenetic control of epiblast maturation leading up to anterior-posterior axis specification. Our study provides a comprehensive molecular model for understanding pluripotent state progressions in vivo during mammalian embryonic development.

Pubmed ID: 29168693 RIS Download

Mesh terms: Animals | Cells, Cultured | Epigenesis, Genetic | Gene Deletion | Gene Expression Regulation, Developmental | Germ Layers | Mice | Nodal Protein | Pluripotent Stem Cells | Signal Transduction | Transcription Factors

Data used in this publication

None found

Associated grants

  • Agency: NCI NIH HHS, Id: P30 CA008748
  • Agency: NIDDK NIH HHS, Id: R01 DK084391
  • Agency: NIGMS NIH HHS, Id: R01 GM095942
  • Agency: NICHD NIH HHS, Id: R21 HD087722

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