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epigenetic histone modification · BEGINNER LESSON

H3K27ac

H3K27ac means histone H3 lysine 27 acetylation, a chemical tag on histone proteins. It is commonly found at active promoters and enhancers and is associated with active transcription.

What it is and what is measured

H3K27ac is a histone modification, meaning a small chemical change on a histone protein that helps package DNA. Here, the measured feature is acetylation on lysine 27 of histone H3, usually detected as enrichment at promoters and enhancers. It is used as a marker of active transcription because regions with H3K27ac often show gene expression, while regions without it are more likely to be inactive or poised. A promoter is a DNA region near a gene start, and an enhancer is a DNA region that helps raise gene activity, often from far away.

[1] Investigating crosstalk between H3K27 acetylation and H3K4 trimethylation in CRISPR/dCas-based epigenome editing and gene activation [2] A narrative review of epigenetic marker in H3K27ac and its ... - PMC [3] Histone H3K27ac separates active from poised enhancers and ...

How it works

Studies in cells show that H3K27ac is written by acetyltransferases such as p300 and CBP. When H3K27ac appears at an enhancer or promoter, it can help recruit reader proteins from the BET family, including BRD2 and BRD4. Readers are proteins that recognize a histone mark and help bring in other machinery needed for transcription, the process of making RNA from DNA. In one editing study, adding H3K27ac at promoters with dCas9-p300 led to later H3K4me3 gain and gene activation, while adding H3K4me3 alone did not create H3K27ac or activate the tested genes. This suggests H3K27ac can act upstream in some cases.

[1] Investigating crosstalk between H3K27 acetylation and H3K4 trimethylation in CRISPR/dCas-based epigenome editing and gene activation [2] A narrative review of epigenetic marker in H3K27ac and its ... - PMC

Why it matters

H3K27ac is widely used as a representative marker of active enhancers and active promoters. In developmental studies, it helped separate active enhancers from poised enhancers, which are enhancer regions that are ready but not fully active. It also helped predict developmental state because H3K27ac-positive enhancers tended to sit near genes with higher expression and more enhancer RNA production. In cancer research, altered H3K27ac has been linked to changes in gene control, but the exact mechanisms are not fully settled.

[2] A narrative review of epigenetic marker in H3K27ac and its ... - PMC [3] Histone H3K27ac separates active from poised enhancers and ...

Limitations

H3K27ac is a useful marker, but it is not a complete explanation for gene control. Some studies show it interacts with other marks such as H3K4me3, and the direction of that interaction is still being studied. Also, H3K27ac does not mean every nearby gene is on, and the presence of the mark alone cannot prove the exact cause of gene activation in every context. Findings can differ across cell types, tissues, and experimental systems.

[1] Investigating crosstalk between H3K27 acetylation and H3K4 trimethylation in CRISPR/dCas-based epigenome editing and gene activation [2] A narrative review of epigenetic marker in H3K27ac and its ... - PMC [3] Histone H3K27ac separates active from poised enhancers and ...

SEE THE IDEA

How H3K27ac can relate to gene activation

p300/CBP can place H3K27ac, readers can bind it, and this can support transcription.

A simple pathway from adding H3K27ac to increased gene activity, with other marks and context affecting the outcome.

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Test your understanding

Choose an answer, then check the explanation.

0 of 3 questions answered
01 Which statement best describes H3K27ac?
02 A researcher adds H3K27ac at a promoter and then sees higher gene expression and later H3K4me3 nearby. What is the best interpretation from the sources?
03 Which result fits an active H3K27ac-marked enhancer?

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Sources and further reading

This general lesson was generated from public source material. It explains a concept; it does not interpret a private paper or provide medical advice.

  1. Investigating crosstalk between H3K27 acetylation and H3K4 trimethylation in CRISPR/dCas-based epigenome editing and gene activation
  2. A narrative review of epigenetic marker in H3K27ac and its ... - PMC
  3. Histone H3K27ac separates active from poised enhancers and ...
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