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Generation of Mice Derived from Induced Pluripotent Stem Cells
Published on: November 29, 2012
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H3.3K122A results in a neomorphic phenotype in mouse embryonic stem cells
Benjamin J Patty1, Cailin Jordan1,2, Santana M Lardo1
1Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA, USA.
Epigenetics & Chromatin
|November 2, 2024
Summary
Mutating histone H3.3K122 in mouse cells created a neomorphic variant, causing lethality. This finding reveals a novel requirement for this globular residue in histone H3.3 viability and transcriptional regulation.
Area of Science:
- Molecular Biology
- Genetics
- Epigenetics
Background:
- Histone H3 and its variant H3.3 are crucial for gene regulation through posttranslational modifications.
- Modifications often occur on histone tails, but globular domain modifications, like H3K122/H3.3K122 acetylation, also play roles.
- Understanding H3.3K122's function is key to deciphering transcriptional regulation.
Purpose of the Study:
- To investigate the function of the H3.3K122 amino acid in transcriptional regulation.
- To generate and analyze mouse embryonic stem (mES) cells with H3.3K122 mutations.
Main Methods:
- Attempted generation of H3.3K122A mES cells.
- Multi-omic profiling of mutant mES cell lines with altered H3.3 alleles.
- Comparative analysis with existing H3.3-null mES cell data.
Main Results:
- H3.3K122A mutation was found to be neomorphic, leading to lethality.
- Contrary to expectations, H3.3-null mES cells are viable but show impaired differentiation.
- A novel dependence on a globular domain residue (H3.3K122) for mES cell viability was uncovered.
Conclusions:
- H3.3K122 is essential for mouse embryonic stem cell viability, challenging previous assumptions.
- The neomorphic nature of H3.3K122A highlights complex roles of histone variants in cellular function.
- This study expands knowledge on histone variants, transcription, and pluripotency regulation in mES cells.
