Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. Involved in muscle maturation via its interaction with the myocyte enhancer factors such as MEF2A, MEF2C and MEF2D.
Defects in HDAC4 are the cause of brachydactyly-mental retardation syndrome (BDMR) [MIM:600430]. A syndrome resembling the physical anomalies found in Albright hereditary osteodystrophy. Common features are mild facial dysmorphism, congenital heart defects, distinct brachydactyly type E, mental retardation, developmental delay, seizures, autism spectrum disorder, and stocky build. Soft tissue ossification is absent, and there are no abnormalities in parathyroid hormone or calcium metabolism.
Belongs to the histone deacetylase family. HD type 2 subfamily.
The nuclear export sequence mediates the shuttling between the nucleus and the cytoplasm.
Phosphorylated by CaMK4 at Ser-246, Ser-467 and Ser-632. Phosphorylation at other residues is required for the interaction with 14-3-3. Sumoylation on Lys-559 is promoted by the E3 SUMO-protein ligase RANBP2, and prevented by phosphorylation by CaMK4.
Nucleus. Cytoplasm. Shuttles between the nucleus and the cytoplasm. Upon muscle cells differentiation, it accumulates in the nuclei of myotubes, suggesting a positive role of nuclear HDAC4 in muscle differentiation. The export to cytoplasm depends on the interaction with a 14-3-3 chaperone protein and is due to its phosphorylation at Ser-246, Ser-467 and Ser-632 by CaMK4. The nuclear localization probably depends on sumoylation.
Detection of HDAC4 in Immunoprecipitates of HeLa whole cell lysates (1 mg for IP, 20% of IP loaded) using ab123513 at 6 µg/mg lysate for IP (Lane 1) and at 1 µg/ml for subsequent Western blot detection. Lane 2 represents control IgG IP.
Detection: Chemiluminescence with an exposure time of 3 seconds.
Western blot - Anti-HDAC4 antibody (ab123513)
All lanes : Anti-HDAC4 antibody (ab123513) at 0.1 µg/ml
Lane 1 : HeLa whole cell lysate at 50 µg Lane 2 : HeLa whole cell lysate at 15 µg Lane 3 : 293T whole cell lysate at 50 µg Lane 4 : Jurkat whole cell lysate at 50 µg