GCN5 is involved in regulation of immunoglobulin heavy chain gene expression in immature B cells

• Published in: Gene Vol. 544; no. 1; pp. 19 - 24
• Main Authors: Kikuchi, Hidehiko, Nakayama, Masami, Kuribayashi, Futoshi, Imajoh-Ohmi, Shinobu, Nishitoh, Hideki, Takami, Yasunari, Nakayama, Tatsuo
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-07-2014
• Subjects: Acetylation; Animals; Avian Proteins - genetics; Avian Proteins - metabolism; Cell Line, Tumor; Chickens; Chromatin - genetics; Chromatin - metabolism; Chromatin Immunoprecipitation; Down-Regulation; DT40; GCN5; Gene Expression Regulation; Gene targeting; Histone acetyltransferase; Histone Acetyltransferases - genetics; Histone Acetyltransferases - metabolism; Histones - metabolism; Immunoblotting; Immunoglobulin; Immunoglobulin Heavy Chains - genetics; Immunoglobulin Heavy Chains - metabolism; Immunoglobulin M - genetics; Immunoglobulin M - metabolism; Lysine - metabolism; Membrane Proteins - genetics; Membrane Proteins - metabolism; Mutation; Precursor Cells, B-Lymphoid - metabolism; Precursor Cells, B-Lymphoid - pathology; Protein Binding; Reverse Transcriptase Polymerase Chain Reaction; GCN5; L-chain; Immunoglobulin; ChIP; DT40; H3K14; Histone acetyltransferase; H-chain; Gene targeting; RT-PCR; H3K9; HAT; GAPDH; HDAC
• ISSN: 0378-1119; 1879-0038
• DOI: 10.1016/j.gene.2014.04.030

GCN5 is involved in the acetylation of core histones, which is an important epigenetic event for transcriptional regulation through alterations in the chromatin structure in eukaryotes. To investigate physiological roles of GCN5, we have systematically analyzed phenotypes of homozygous GCN5-deficient DT40 mutants. Here, we report participation of GCN5 in regulation of IgM heavy chain (H-chain) gene expression. GCN5-deficiency down-regulates gene expressions of IgM H-chain (as whole, membrane-bound and secreted forms of its mRNA) but not light chain (L-chain), causing decreases in membrane-bound and secreted forms of IgM proteins. Chromatin immnoprecipitation assay revealed that GCN5 binds to the chicken IgM H-chain gene around its constant region but not L-chain gene, and acetylate Lys-9 residues of histone H3 within chromatin surrounding the constant region. These results suggest that GCN5 takes part in transcriptional regulation of the IgM H-chain gene via histone acetylation resulting in formation of relaxed chromatin arrangement around its coding region and plays a key role in epigenetic regulation of B cell functions.
•GCN5-deficiency caused remarkable decrease in cell surface membrane-bound IgM protein.•GCN5-deficiency caused remarkable decrease in secreted IgM protein in culture media.•GCN5-deficiency down-regulated transcription of IgM H-chain but not L-chain.•GCN5 bound to the constant region of the IgM H-chain gene but not L-chain gene.•GCN5 probably constructs euchromatin around coding region of the IgM H-chain gene.