Identification and roles in inflammatory processes of the histone deacetylase family genes in the jawless vertebrate lamprey (Lethenteron camtschaticum).

Abstract

Acetylation affects the activity and function of cytokines and transcription factors that are associated with inflammation. Histone deacetylases (HDACs) are involved in chromatin remodelling and regulate cellular processes by removing acetyl groups from histones. In this study, six HDAC family genes, HDAC1, HDAC3, HDAC4, HDAC6, HDAC10, and HDAC11, were screened and cloned from the most primitive vertebrate lamprey, Lethenteron camtschaticum. Bioinformatic analysis revealed that HDACs of lamprey are relatively conserved in domains, motifs, gene structure and the three-dimensional (3D) structure compared to those of higher vertebrates. Analysis of expression distribution revealed that HDACs in lamprey are commonly expressed in all tissues, particularly the gonads. Lc-HDACs showed up-regulation and down-regulation in the leukocytes of lampreys stimulated by LPS for 4 h, 12 h and 24 h. Lc-HDAC4 was up-regulated at all LPS stimulation time points, while Lc-HDAC6 was completely opposite. Cell overexpression, luciferase reporter assays and qPCR for detection of inflammatory factor levels showed that the regulatory role of HDACs in inflammation is conserved in lampreys compared to higher vertebrates. Our study successfully clarified the characterization and function of HDACs in primitive vertebrates, and also provided valuable insights into the inflammatory response in jawless vertebrates.