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Is H3K4me3 instructive for transcription activation?
Françoise S Howe1, Harry Fischl1, Struan C Murray1
1Department of Biochemistry, University of Oxford, Oxford, UK.
Summary
Tri-methylation of lysine 4 on histone H3 (H3K4me3) is a result of gene transcription, not a cause. This epigenetic mark influences transcriptional memory and consistency, rather than directly instructing gene activity.
Area of Science:
- Epigenetics
- Molecular Biology
- Gene Regulation
Background:
- Tri-methylation of lysine 4 on histone H3 (H3K4me3) is a conserved epigenetic mark found at active gene promoters.
- H3K4me3 is widely considered an 'activating' histone modification, presumed to instruct gene transcription.
Purpose of the Study:
- To investigate the causal role of H3K4me3 in gene transcription.
- To explore the functional consequences of H3K4me3 deposition in chromatin.
Main Methods:
- Genome-wide studies analyzing transcriptional changes upon H3K4me3 removal.
- Time-resolved experiments to observe H3K4me3 dynamics relative to transcription.
Main Results:
- Little change in gene transcription was observed upon significant reduction of H3K4me3 under various conditions.
- H3K4me3 deposition was found to be a consequence of transcription, not a prerequisite.
- H3K4me3 influences transcriptional memory, cellular consistency, and termination.
Conclusions:
- H3K4me3 does not play a major instructive role in initiating gene transcription.
- H3K4me3 functions as a readout of transcriptional activity, impacting downstream processes like epigenetic memory and transcriptional fidelity.
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