HDAC8 regulates neural differentiation through embryoid body formation in P19 cells

  • Biochem Biophys Res Commun. 2018 Mar 25;498(1):45-51. doi: 10.1016/j.bbrc.2018.02.195.
Syouichi Katayama  1 ,  Atsushi Morii  1 ,  Juliet O Makanga  1 ,  Takayoshi Suzuki  2 ,  Naoki Miyata  3 ,  Tetsuya Inazu  4
Affiliations
  • 1. Department of Pharmacy, College of Pharmaceutical Sciences, Ritsumeikan University, Kusatsu, Shiga 525-8577, Japan.
  • 2. Graduate School of Medical Sciences, Kyoto Prefectural University of Medicine, Sakyo-ku, Kyoto 606-0823, Japan; CREST, Japan Science and Technology Agency (JST), Kawaguchi, Saitama 332-0012, Japan.
  • 3. Institute of Drug Discovery Science, Nagoya City University, Mizuho-ku, Nagoya 467-8603, Japan.
  • 4. Department of Pharmacy, College of Pharmaceutical Sciences, Ritsumeikan University, Kusatsu, Shiga 525-8577, Japan. Electronic address: [email protected].
PMID: 29499194 DOI: 10.1016/j.bbrc.2018.02.195
Abstract

Histone acetylation and deacetylation correlate with diverse biological phenomena through gene transcription. Histone deacetylases (HDACs) regulate deacetylation of histones and Other proteins. However, as a member of the HDAC family, HDAC8 function during neurodevelopment is currently unknown. Therefore, we investigated HDAC8 function during neurodevelopment by examining embryoid body (EB) formation in P19 cells. HDAC8-selective inhibitor (NCC-149) (HDAC8i)-treated cells showed smaller EBs than non-treated cells, as well as reduced expression levels of the neuronal marker, NeuN. Additionally, HDAC8i treatment led to inhibition of cellular proliferation by G2/M phase accumulation and downregulated cyclin A2 and cyclin B1 gene expression. Furthermore, two independent HDAC8 knockout cell lines were established by CRISPR-Cas9, which resulted in smaller EBs, similar to HDAC8i-treated cells. These results suggest that HDAC8 regulates neural differentiation by exerting control of EB formation.

Keywords
CRISPR-Cas9; Cell cycle; HDAC8; HDAC8-Selective inhibitor; NCC-149; Neurodevelopment.
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