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H3K9me selectively blocks transcription factor activity and ensures differentiated tissue integrity
Stephen P Methot1, Jan Padeken1, Giovanna Brancati1,2
1Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
Nature Cell Biology
|November 5, 2021
Summary
Histone H3K9 methylation (H3K9me) regulates gene expression during development. Loss of H3K9me causes specific gene upregulation, while its deposition maintains differentiated cell function by restricting transcription factors.
Area of Science:
- Epigenetics
- Developmental Biology
- Molecular Biology
Background:
- The role of histone H3K9 methylation (H3K9me), a hallmark of heterochromatin, in development is not fully understood.
- H3K9me is dynamically regulated during development, with distinct patterns observed in different tissues and developmental stages.
- The SETDB1 homolog MET-2 is responsible for continuous H3K9me2 deposition after terminal differentiation in C. elegans.
Purpose of the Study:
- To investigate the developmental function of histone H3K9 methylation (H3K9me).
- To elucidate the mechanisms by which H3K9me regulates gene expression in differentiated tissues.
- To understand the relationship between H3K9me, chromatin accessibility, and gene transcription.
Main Methods:
- Analysis of gene expression patterns in Caenorhabditis elegans with altered H3K9me levels.
- Chromatin accessibility assays (ATAC-seq) to assess the impact of H3K9me on DNA accessibility.
- Investigation of transcription factor activity in relation to H3K9me and gene expression.
Main Results:
- Loss of H3K9me leads to tissue- and stage-specific gene upregulation.
- H3K9me is lost from differentiated cell-type-specific genes during development and gained at genes for earlier stages or other tissues.
- H3K9me restricts transcription factor activity at promoters and enhancers, ensuring gene silencing in differentiated tissues.
- Increased chromatin accessibility is not always sufficient or necessary for transcription upon H3K9me loss.
- Derepressed genes near the nuclear periphery remain poorly accessible despite transcription.
Conclusions:
- Histone H3K9 methylation plays a crucial role in conferring tissue-specific gene expression.
- H3K9me maintains the integrity of terminally differentiated muscle by restricting transcription factor activity.
- The dynamic deposition and removal of H3K9me are essential for proper developmental gene regulation.
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