HDAC Regulates Transcription at the Outset of Axolotl Tail Regeneration

Scientific Reports, 2019 · DOI: 10.1038/s41598-019-43230-6 · Published: May 7, 2019

Genetics Regenerative Medicine & Stem Cells

Simple Explanation

Tissue regeneration involves complex changes in gene expression and protein modifications. Researchers tested compounds targeting epigenetic mechanisms in axolotl embryos during tail regeneration. HDAC activity is required at the time of tail amputation to regulate the initial transcriptional response to injury and regeneration.

Study Duration

7 days

Participants

Axolotl embryos

Evidence Level

Not specified

Key Findings

1
A chemical screen identified 55 chemicals that inhibited axolotl tail regeneration, with histone deacetylase inhibitors (HDACi) being highly represented.
2
Romidepsin, an FDA-approved anticancer drug, potently inhibited tail regeneration when embryos were treated continuously for 7 days or even with a brief 1-minute post-amputation treatment.
3
Microarray analysis revealed that romidepsin altered early transcriptional responses at 3 and 6 hours post-amputation, affecting genes involved in tumor cell death, transcription regulation, cell differentiation, and tissue morphogenesis.

Research Summary

This study investigates the role of epigenetic mechanisms, specifically histone deacetylases (HDACs), in axolotl tail regeneration using a chemical genetic screen. The screen identified several HDAC inhibitors that significantly inhibited tail regeneration, with romidepsin showing potent effects even with short exposure times. Microarray analysis of romidepsin-treated embryos revealed altered gene expression patterns at early post-amputation time points, affecting key regulatory genes and signaling pathways involved in regeneration.

Practical Implications

Epigenetic Regulation of Regeneration

Highlights the importance of epigenetic modifications, particularly HDAC activity, in regulating the early transcriptional response to injury and regeneration.

Potential Therapeutic Targets

Identifies HDAC inhibitors, such as romidepsin, as potential targets for manipulating regeneration processes, although further research is needed to understand the cell-type specificity and context-dependent effects.

Conservation of Mechanisms

Suggests that cancer and tissue regeneration may share common epigenetic regulatory mechanisms, offering insights into potential therapeutic strategies for both fields.

Study Limitations

1
The study focused primarily on HDAC inhibitors; further research is needed to explore the role of other epigenetic modifiers in regeneration.
2
The mechanisms by which romidepsin affects specific cell types and signaling pathways during regeneration require further investigation.
3
The long-term effects of HDAC inhibition on axolotl tail regeneration and the potential for compensatory mechanisms were not fully explored.

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