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Updated: May 20, 2026
10:28
Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers
Published on: September 20, 2018
Making a noisy gene: HDACs turn up the static
Roshan M Kumar1, James J Collins
1Howard Hughes Medical Institute, Department of Biomedical Engineering and Center for BioDynamics, Boston University, Boston, MA 02215, USA.
Molecular Cell
|July 31, 2012
Summary
Specific histone deacetylases (HDACs) control distinct transcription stages. This reveals how chromatin dynamics generate gene-specific noise in identical cells.
Area of Science:
- Molecular biology
- Epigenetics
- Gene regulation
Background:
- Gene expression exhibits variability even in genetically identical cells, a phenomenon known as noise.
- Histone deacetylases (HDACs) are enzymes that remove acetyl groups from histones, influencing chromatin structure and gene accessibility.
Discussion:
- Weinberger et al. demonstrate that different HDACs target specific steps in the transcription process.
- This regulation by HDACs is crucial for controlling the variability of gene expression at the single-cell level.
Key Insights:
- Specific HDACs play distinct roles in regulating transcription.
- Chromatin dynamics, modulated by HDACs, are a key factor in generating cell-to-cell differences in gene expression.
- Understanding HDAC function provides insights into the mechanisms of transcriptional noise.
Outlook:
- Further research can elucidate the precise mechanisms by which individual HDACs affect different transcriptional stages.
- Targeting specific HDACs could offer novel strategies for modulating gene expression variability in various biological contexts.
- Investigating the interplay between HDACs and other epigenetic modifiers may reveal complex regulatory networks governing transcriptional noise.
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The histone proteins in the nucleosomes are post-translationally modified (PTM) to increase or decrease access to DNA. The commonly observed PTMs are methylation, acetylation, phosphorylation, and ubiquitination of lysine amino acids in the histone H3 tail region. These histone modifications have specific meaning for the cell. Hence, they are called "histone code". The protein complex involved in histone modification is termed as "reader-writer" complex.
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02:32Position-effect Variegation
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02:32Histone Modification
The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
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02:46Genome Copying Errors
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The extent of chromatin compaction can be studied by staining chromatin using specific DNA binding dyes. Under the microscope, the dense-compacted regions that take up more dye are called heterochromatin. Heterochromatin is further classified into two forms – constitutive heterochromatin and facultative heterochromatin.
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