Histone acetyltransferase PCAF is involved in transactivation of Bcl-6 and Pax5 genes in immature B cells.
Histone acetyltransferase PCAF is involved in transactivation of Bcl-6 and Pax5 genes in immature B cells.
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DOI：
10.1016/j.bbrc.2015.10.011
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发表时间：
2015-11
影响因子：
3.1
通讯作者：
H. Kikuchi;Masami Nakayama;F. Kuribayashi;H. Mimuro;S. Imajoh‐ohmi;H. Nishitoh;T. Nakayama
中科院分区：
文献类型：
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作者：
H. Kikuchi;Masami Nakayama;F. Kuribayashi;H. Mimuro;S. Imajoh‐ohmi;H. Nishitoh;T. Nakayama
组蛋白乙酰转移酶p300/CBP相关因子(PCAF)属于GCN5家族，通过改变染色质结构来调节各种表观遗传事件的转录调控。在B细胞的正常发育过程中，许多转录因子的基因表达受到包括组蛋白乙酰化和去乙酰化在内的表观遗传机制的严格调控，以完成其发育途径。在这里，我们通过分析PCAF缺失的DT40突变体ΔPcaF，我们报道了PcaF参与了B细胞淋巴瘤-6(Bcl6)和配对盒基因5(Pax5)的转录激活，这两个基因是B细胞正常发育所必需的转录因子。PCAF缺乏导致Bcl6和Pax5基因表达水平显著降低，而B淋巴细胞诱导成熟蛋白1(Blimp 1)基因表达水平显著升高。此外，染色质免疫沉淀分析表明，体内PCAF缺乏导致Bcl6和Pax5基因5‘侧翼区域染色质中H3K9和H3K14残基的乙酰化水平显著降低，表明它们的基因表达可能受到PCAF的调控。这些结果表明，PCAF参与了Bcl6和Pax5基因的反式激活，导致Blimp-1基因表达下调，并在B细胞发育的表观遗传调控中发挥关键作用。
Histone acetyltransferase p300/CBP-associated factor (PCAF) belonging to GCN5 family regulates various epigenetic events for transcriptional regulation through alterations in the chromatin structure. During normal development of B cells, gene expressions of numerous transcription factors are strictly regulated by epigenetic mechanisms including histone acetylation and deacetylation to complete their development pathways. Here, by analyzing PCAF-deficient DT40 mutants, ΔPCAF, we report that PCAF takes part in transcriptional activation of B cell lymphoma-6 (Bcl-6) and Paired box gene 5 (Pax5), which are essential transcription factors for normal development of B cells. PCAF-deficiency caused drastic decrease in mRNA levels of Bcl-6 and Pax5, and remarkable increase in that of B lymphocyte-induced maturation protein-1 (Blimp-1). In addition, chromatin immunoprecipitation assay showed that PCAF-deficiency caused remarkable decrease in acetylation levels of both H3K9 and H3K14 residues within chromatin surrounding the 5’-flanking regions of Bcl-6 and Pax5 genesin vivo, suggesting that their gene expressions may be regulated by PCAF. These results revealed that PCAF is involved in transactivation of Bcl-6 and Pax5 genes, resulting in down-regulation of Blimp-1 gene expression, and plays a key role in epigenetic regulation of B cell development.