HDAC4

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 II of the histone deacetylase/acuc/apha family. It possesses histone deacetylase activity and represses transcription when tethered to a promoter. This protein does not bind DNA directly but through transcription factors MEF2C and MEF2D. It seems to interact in a multiprotein complex with RbAp48 and HDAC3. Furthermore, HDAC4 is required for TGFbeta1-induced myofibroblastic differentiation.

Clinical significance

Studies have shown that HDAC4 regulates bone and muscle development. Harvard University researchers also concluded that it promotes healthy vision: Reduced levels of the protein led to the death of the rod photoreceptors and bipolar cells in the retinas of mice.

Interactions

HDAC4 has been shown to interact with:

• BCL6,
• BTG2,
• CBX5,
• GATA1,
• HDAC3,
• MAPK1,
• MAPK3,
• MEF2C,
• Myocyte-specific enhancer factor 2A,
• Nuclear receptor co-repressor 1,
• Nuclear receptor co-repressor 2,
• Testicular receptor 2,
• YWHAB,
• YWHAE, and
• Zinc finger and BTB domain-containing protein 16.

References

References

1. (April 1999). "Three proteins define a class of human histone deacetylases related to yeast Hda1p". Proceedings of the National Academy of Sciences of the United States of America.
2. (April 1999). "A new family of human histone deacetylases related to Saccharomyces cerevisiae HDA1p". The Journal of Biological Chemistry.
3. "Entrez Gene: HDAC4 histone deacetylase 4".
4. (October 2007). "Histone deacetylase 4 is required for TGFbeta1-induced myofibroblastic differentiation". Biochimica et Biophysica Acta (BBA) - Molecular Cell Research.
5. ''Protein for Sight'', [[Scientific American]], '''300''', 3 (March 2009), p. 23
6. (January 2009). "HDAC4 regulates neuronal survival in normal and diseased retinas". Science.
7. (July 2007). "Inhibition of medulloblastoma tumorigenesis by the antiproliferative and pro-differentiative gene PC3". FASEB Journal.
8. (July 2017). "HDAC1, HDAC4, and HDAC9 Bind to PC3/Tis21/Btg2 and Are Required for Its Inhibition of Cell Cycle Progression and Cyclin D1 Expression". Journal of Cellular Physiology.
9. (October 2002). "Association of class II histone deacetylases with heterochromatin protein 1: potential role for histone methylation in control of muscle differentiation". Molecular and Cellular Biology.
10. (December 2003). "Altered interaction of HDAC5 with GATA-1 during MEL cell differentiation". Oncogene.
11. (September 2001). "Human HDAC7 histone deacetylase activity is associated with HDAC3 in vivo". The Journal of Biological Chemistry.
12. (December 2000). "Histone deacetylase 4 associates with extracellular signal-regulated kinases 1 and 2, and its cellular localization is regulated by oncogenic Ras". Proceedings of the National Academy of Sciences of the United States of America.
13. (November 1999). "HDAC4, a human histone deacetylase related to yeast HDA1, is a transcriptional corepressor". Molecular and Cellular Biology.
14. (September 2001). "Histone deacetylase 4 possesses intrinsic nuclear import and export signals". Molecular and Cellular Biology.
15. (September 1999). "HDAC4 deacetylase associates with and represses the MEF2 transcription factor". The EMBO Journal.
16. (May 2000). "mHDA1/HDAC5 histone deacetylase interacts with and represses MEF2A transcriptional activity". The Journal of Biological Chemistry.
17. (January 2002). "Enzymatic activity associated with class II HDACs is dependent on a multiprotein complex containing HDAC3 and SMRT/N-CoR". Molecular Cell.
18. (January 2000). "Nuclear receptor corepressors partner with class II histone deacetylases in a Sin3-independent repression pathway". Genes & Development.
19. (August 2003). "Interaction of nuclear receptor zinc finger DNA binding domains with histone deacetylase". Molecular and Cellular Endocrinology.
20. (August 2001). "The orphan nuclear receptor TR2 interacts directly with both class I and class II histone deacetylases". Molecular Endocrinology.
21. (July 2000). "Regulation of histone deacetylase 4 and 5 and transcriptional activity by 14-3-3-dependent cellular localization". Proceedings of the National Academy of Sciences of the United States of America.
22. (August 2001). "Differential localization of HDAC4 orchestrates muscle differentiation". Nucleic Acids Research.
23. (June 2002). "Class II histone deacetylases are directly recruited by BCL6 transcriptional repressor". The Journal of Biological Chemistry.
24. (November 2004). "HDAC4 mediates transcriptional repression by the acute promyelocytic leukaemia-associated protein PLZF". Oncogene.