HDAC8

Cilia effects upon perturbation of HDAC8

Cilia number / % ciliated:

Decreased cilia number

Loss-of-function effect:

Shorter cilia

Ciliogenesis screen results (4 screens)

• Kim2016: Not Reported
• Wheway et al. 2015 (siRNA) [siRNA]: Ciliogenesis Defect (z=-5.68) PMID:26167766
• Breslow et al. 2018 (CRISPR) [CRISPR]: Negative Regulator (Hh signaling, casTLE effect=0.74) PMID:29459680
• Roosing et al. 2015 (siRNA) [siRNA]: Hyper-ciliogenesis (robust z=2.81, ciliated=59.1%) PMID:26595381

Phenotypes

Mouse phenotype:

decreased body length, increased circulating magnesium level, increased circulating alkaline phosphatase level, decreased bone mineral density, decreased bone mineral content

Mouse ciliopathy phenotype:

increased circulating aspartate transamise level, increased circulating alanine transamise level

Human ciliopathy phenotype:

Intellectual disability

Ciliopathy associations

• Cornelia de Lange Syndrome

Subcellular localization

cilia associated gene, cytosol, nucleus

Functional category

• Ciliary assembly/disassembly
• Protein processing & maturation
• Signaling (Hedgehog, GPCRs, ion channels)
• Transcription regulation

Function

Mutations in the HDAC8 gene cause Cornelia de Lange Syndrome (PMID: 22885700). The number of cells with cilia was significantly reduced in HDAC3- and HDAC8-depleted cells. The ciliary length also decreased in HDAC3- and HDAC8-depleted cells compared to control cells. A knockdown-rescue experiment showed that wild-type HDAC3 and HDAC8 rescued the cilia assembly and ciliary length in HDAC3- and HDAC8-depleted cells, respectively, deacetylase-dead HDAC3 and HDAC8 mutants did not. (31362948)