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Cell-type-specific control of enhancer activity by H3K9 trimethylation
Yina Zhu1, Dominic van Essen, Simona Saccani
1Department of Cellular and Molecular Immunology, Max Planck Institute for Immunobiology and Epigenetics, Freiburg, Germany.
Molecular Cell
|May 29, 2012
Summary
Cell-type-specific gene expression relies on H3K9me3 repression. The demethylase Jmjd2d activates genes in immune cells by removing this repression, a mechanism vital for multicellular development.
Area of Science:
- Molecular Biology
- Epigenetics
- Developmental Biology
Background:
- Cell-type-specific gene expression is essential for multicellular organism development.
- Understanding the regulatory mechanisms controlling this specificity is crucial.
Purpose of the Study:
- To investigate the mechanisms underlying cell-type-specific gene expression control.
- To identify regulatory elements and factors responsible for restricting gene expression to specific immune cells.
Main Methods:
- Studied regulation of model genes Mdc and Il12b in immune cells.
- Analyzed promoter and enhancer sequences for cell-type specificity.
- Performed genome-wide analysis of H3K9 trimethylation (H3K9me3) patterns.
- Investigated the role of Jmjd2d demethylase in regulating H3K9me3 levels.
Main Results:
- Neither promoter nor enhancer sequences alone conferred cell-type specificity.
- Upstream enhancers were repressed in non-expressing cells by high H3K9me3 levels.
- H3K9me3-mediated repression was identified as a common regulatory mechanism for cell-type-specific genes.
- Jmjd2d demethylase was required for Mdc and Il12b transcription in dendritic cells and macrophages by controlling H3K9me3.
Conclusions:
- H3K9me3-mediated repression is a widespread mechanism for achieving cell-type specificity.
- This mechanism allows broadly functional enhancers to be specifically regulated.
- Jmjd2d plays a key role in activating cell-type-specific gene expression in immune cells.
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