Histone H4 deacetylation plays a critical role in early gene silencing during neuronal apoptosis
| Autor: | Heather R. Pelzel, Cassandra L. Schlamp, Robert W. Nickells |
|---|---|
| Jazyk: | angličtina |
| Předmět: |
Retinal Ganglion Cells
Chromatin Immunoprecipitation Blotting Western Fluorescent Antibody Technique Apoptosis Retinal ganglion Histone Deacetylases lcsh:RC321-571 Histone H4 Histones 03 medical and health sciences Mice Cellular and Molecular Neuroscience 0302 clinical medicine Research article medicine Gene silencing Animals Gene Silencing lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry 030304 developmental biology 0303 health sciences biology Reverse Transcriptase Polymerase Chain Reaction General Neuroscience lcsh:QP351-495 Acetylation HDAC3 Molecular biology Chromatin Cell biology lcsh:Neurophysiology and neuropsychology Trichostatin A Histone Optic Nerve Injuries biology.protein sense organs Chromatin immunoprecipitation 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | BMC Neuroscience BMC Neuroscience, Vol 11, Iss 1, p 62 (2010) |
| ISSN: | 1471-2202 |
| DOI: | 10.1186/1471-2202-11-62 |
| Popis: | Background Silencing of normal gene expression occurs early in the apoptosis of neurons, well before the cell is committed to the death pathway, and has been extensively characterized in injured retinal ganglion cells. The causative mechanism of this widespread change in gene expression is unknown. We investigated whether an epigenetic change in active chromatin, specifically histone H4 deacetylation, was an underlying mechanism of gene silencing in apoptotic retinal ganglion cells (RGCs) following an acute injury to the optic nerve. Results Histone deacetylase 3 (HDAC3) translocates to the nuclei of dying cells shortly after lesion of the optic nerve and is associated with an increase in nuclear HDAC activity and widespread histone deacetylation. H4 in promoters of representative genes was rapidly and indiscriminately deacetylated, regardless of the gene examined. As apoptosis progressed, H4 of silenced genes remained deacetylated, while H4 of newly activated genes regained, or even increased, its acetylated state. Inhibition of retinal HDAC activity with trichostatin A (TSA) was able to both preserve the expression of a representative RGC-specific gene and attenuate cell loss in response to optic nerve damage. Conclusions These data indicate that histone deacetylation plays a central role in transcriptional dysregulation in dying RGCs. The data also suggests that HDAC3, in particular, may feature heavily in apoptotic gene silencing. |
| Databáze: | OpenAIRE |
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