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Histone Epigenetic Signatures in Embryonic Limb Interdigital Cells Fated to Die
Cristina Sanchez-Fernandez1, Carlos I Lorda-Diez1, Cristina Duarte-Olivenza1
1Departamento de Anatomía y Biología Celular, Instituto de Investigación Sanitaria Marqués de Valdecilla (IDIVAL), Universidad de Cantabria, 39011 Santander, Spain.
Cells
|April 30, 2021
Summary
Epigenetic modifications in limb development influence DNA damage and cell death. Histone methylation patterns correlate with DNA damage, preceding apoptosis during interdigital tissue regression.
Area of Science:
- Developmental Biology
- Epigenetics
- Cell Biology
Background:
- Vertebrate limb development involves interdigital mesoderm elimination via apoptosis and cell senescence.
- This regression is preceded by DNA damage and activation of DNA repair pathways.
Purpose of the Study:
- To investigate the role of epigenetic modifications in interdigital mesoderm degeneration.
- To understand the relationship between histone modifications, DNA methylation, and cell death during tissue remodeling.
Main Methods:
- Analysis of histone trimethylation (H3K4me3, H3K9me3, H3K27me3) and 5-methylcytosine (5mC) in interdigital cells.
- Assessment of acetylated histones (H3K9ac, H4ac) and histone variant H3.3 distribution.
- Gene expression analysis of histone deacetylase (HDAC) genes.
- Pharmacological inhibition of histone deacetylases using trichostatin A.
Main Results:
- Trimethylated histone 3 patterns overlap with 5-methylcytosine in interdigital cell nuclei.
- Histone deacetylase genes (HDAC1, HDAC2, HDAC3, HDAC8, HDAC10) are expressed in interdigits.
- Inhibition of histone deacetylases with trichostatin A induced cell death and transcriptional changes preceding physiological tissue regression.
Conclusions:
- Epigenetic profiles, specifically histone methylation patterns, are associated with DNA damage sensitivity in interdigital mesoderm.
- Histone deacetylase activity plays a crucial role in regulating chromatin state and influencing cell fate during tissue regression.
- These findings suggest epigenetic mechanisms contribute to programmed cell death in limb development.
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