GCN5 is involved in regulation of immunoglobulin heavy chain gene expression in immature B cells.
GCN5 is involved in regulation of immunoglobulin heavy chain gene expression in immature B cells.
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GCN5 参与未成熟 B 细胞中免疫球蛋白重链基因表达的调节。
DOI：
10.1016/j.gene.2014.04.030
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发表时间：
2014
期刊：
影响因子：
3.5
通讯作者：
Nakayama T.
中科院分区：
文献类型：
--
作者：
Kikuchi H.;Nakayama M.;Kuribayashi F.;Imajoh-Ohmi S.;Nishitoh H.;Takami Y.;Nakayama T.
GCN5 参与核心组蛋白的乙酰化，这是真核生物中通过改变染色质结构进行转录调控的重要表观遗传事件。为了研究 GCN5 的生理作用，我们系统分析了纯合 GCN5 缺陷 DT40 突变体的表型。在这里，我们报道了 GCN5 参与 IgM 重链（H 链）基因表达的调节。 GCN5 缺陷会下调 IgM H 链（整体、其 mRNA 的膜结合和分泌形式）的基因表达，但不会下调轻链（L 链），导致 IgM 蛋白的膜结合和分泌形式减少。染色质免疫沉淀分析显示，GCN5 与恒定区周围的鸡 IgM H 链基因结合，但不与 L 链基因结合，并乙酰化恒定区周围染色质内组蛋白 H3 的 Lys-9 残基。这些结果表明，GCN5 通过组蛋白乙酰化参与 IgM H 链基因的转录调节，导致其编码区周围形成松弛的染色质排列，并在 B 细胞功能的表观遗传调节中发挥关键作用。
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.