Histone deacetylases (HDACs) participate in the deacetylation of core histones, which is an important event in transcription regulation through alterations in the chromatin structure. We cloned cDNAs and genomic DNAs encoding two chicken HDACs (chHDAC-1 and 2), which are preferentially localized in nuclei. Using gene targeting techniques, we generated homozygous DT40 mutants, ΔchHDAC-1 and 2, devoid of two alleles of chHDAC-1 and 2 genes, respectively. The protein patterns on 2D-PAGE obviously changed for ΔchHDAC-2, and the amounts of the IgM H and L-chains increased in it. Of the two IgM H-chain forms, the secreted form (μ s) increased in ΔchHDAC-2, but the membrane-bound form (μ m) decreased. The IgM H-chain gene was transcribed more in ΔchHDAC-2 than in DT40 cells. In the mutant, the alternative processing of IgM H-chain pre-mRNA preferentially occurred, resulting in an increase in the amount of μs mRNA. Based on these results, we propose a model for a role of chHDAC-2 in both the transcription and alternative processing steps, resulting in control of the amount of the μs IgM H-chain.
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