HDAC8

Function

Histones play a critical role in transcriptional regulation, cell cycle progression, and developmental events. Histone acetylation / deacetylation alters chromosome structure and affects transcription factor access to DNA. The protein encoded by this gene belongs to class I of the histone deacetylase/acuc/apha family. It has histone deacetylase activity and represses transcription when tethered to a promoter.

Histone deacetylase 8 is involved in skull morphogenesis and metabolic control of the ERR-alpha / PGC1-alpha transcriptional complex.

Clinical significance

HDAC8 has been linked to number of disease states notably to acute myeloid leukemia and is related to actin cytoskeleton in smooth muscle cells. siRNA targeting HDAC8 showed anticancer effects. Inhibition of HDAC8 induced apoptosis has been observed in T cell lymphomas. In addition the HDAC8 enzyme has been implicated in the pathogenesis of neuroblastoma. Therefore, there has been interest in developing HDAC8 selective inhibitors. At least 20 disease-causing mutations in this gene have been discovered.

Interactions

• ERR-alpha.

References

References

1. (May 2000). "Characterization of a highly complex region in Xq13 and mapping of three isodicentric breakpoints associated with preleukemia". Genomics.
2. (Aug 2000). "Cloning and characterization of human histone deacetylase 8". FEBS Lett.
3. "Entrez Gene: HDAC8 histone deacetylase 8".
4. (July 2009). "Epigenetic control of skull morphogenesis by histone deacetylase 8". Genes Dev..
5. (July 2010). "An acetylation switch modulates the transcriptional activity of estrogen-related receptor alpha". Mol. Endocrinol..
6. (March 2007). "HDACs, histone deacetylation and gene transcription: from molecular biology to cancer therapeutics". Cell Res..
7. (May 2008). "A novel histone deacetylase 8 (HDAC8)-specific inhibitor PCI-34051 induces apoptosis in T-cell lymphomas". Leukemia.
8. (January 2009). "Histone deacetylase 8 in neuroblastoma tumorigenesis". Clin. Cancer Res..
9. (May 2013). "3-Hydroxypyridin-2-thione as novel zinc binding group for selective histone deacetylase inhibition". Journal of Medicinal Chemistry.
10. (November 2012). "Rapid discovery of highly potent and selective inhibitors of histone deacetylase 8 using click chemistry to generate candidate libraries". Journal of Medicinal Chemistry.
11. (December 2019). "Refinement of evolutionary medicine predictions based on clinical evidence for the manifestations of Mendelian diseases". Scientific Reports.