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Toggling the functions of a protein that regulates gene expression during cellular reprogramming ensures cell fate conversion, an A*STAR study has found.
Understanding how cell fate is maintained is key for improving the efficiency with which induced pluripotent stem cells, iPSCs, can be derived from patients' somatic cells and differentiated into tissue-specific cell types for the treatment of medical conditions such as leukemia or spinal cord injury.
Histone - Variant - H3 - Protein - Gene
The histone variant, H3.3, is a protein that has previously been shown to activate gene transcription during cellular differentiation, but its exact role in cell fate transition was unclear. Jonathan Yuin-Han Loh at the A*STAR Institute of Molecular and Cell Biology in Singapore and colleagues have investigated the effect of H3.3 in the transformation of mouse embryonic fibroblasts into iPSCs and hematopoietic progenitor cells, as well as in the differentiation of stem cells into neurons.
In all three scenarios they found that H3.3 has a dual role: it maintains parent cell identity in the early stages of reprogramming, and aids cell fate transition at later stages. This switch in function is regulated by the histone chaperone Hira, which deposits H3.3 on specific DNA regions, and an epigenetic modification involving the addition of methyl groups to two lysine residues. "Our results were both surprising and unexpected, because H3.3 seems to work...
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