Histone modifications across the cell cycle in undifferentiated and differentiating mouse embryonic stem cells

Goss, Hannah Myren (2014). Histone modifications across the cell cycle in undifferentiated and differentiating mouse embryonic stem cells. University of Birmingham. Ph.D.

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Abstract

The role of post translational histone modifications in stem cells has been of increasing interest in recent years, however, the heritability of histone modifications has not yet been determined, and as such their status as epigenetic remains in question. Here we have taken the novel approach of comparing the enrichment of histone modifications, across specific genes and how they are modulated through various phases of the cell cycle: in doing so we address this question of heritability from a new perspective.

Highly dynamic fluctuations in the enrichment of histone modifications were observed across the cell cycle in embryonic stem cells. In cell cycle regulated genes the patterns of modification enrichment revealed an increase in active marks either pre-emptive or at the point of expression, indicative of highly dynamic regulation, not a stable heritable transmission, perhaps reflective of the plasticity of these cells. Following on from this embryonic stem cells were differentiated for seven days, allowing the enforcement of canonical cell cycle regulation and a more lineage specific transcription profile. At this point histone modifications displayed a variety of patterns including what appeared to be the stable and presumably heritable transmission of H3K4me3 and H3K27me3 across the cell cycle.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

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