The role of transcription and splicing on histone H3 lysine 4 trimethylation dynamics

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Date
2017
Authors
Lau, Veronica
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Abstract
Histone H3 lysine 4 trimethylation (H3K4me3) is a histone post-translational modification that is normally located near the transcription start site and first 5’ splice site of a gene. Enzymes are involved in regulating the addition and removal of H3K4me3 along the length of the gene body. However, little is understood about these changes during transcriptional induction. Additionally, the effects of splicing inhibition have not been examined in an endogenous system. We hypothesized that transcription and pre-mRNA splicing at the 5’ coding region plays a role in H3K4me3 dynamics. Chromatin immunoprecipitation assays ± splicing (isoginkgetin) or transcription (5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole) inhibitors were done to determine the H3K4me3 levels along the immediate early gene Fos. The gene was stimulated with epidermal growth factor, and monitored at various times. H3K4me3 levels increased and decreased along the induced Fos gene. Inhibition of transcription or splicing prevented these changes in H3K4me3 levels during transcription, suggesting that splicing may influence H3K4me3 levels indirectly. The significance of these finding is that it provides a better understanding of how H3K4me3 is regulated during transcription and splicing of a gene.
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Keywords
H3K4me3, Transcription, Pre-mRNA splicing
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