酪氨酸蛋白激酶Btk在B細胞受體信號傳導中起重要作用。Btk基因突變導致人與小鼠發生免疫缺陷。該項研究揭示了Btk轉錄調節的新機制—組蛋白乙酰轉移酶p300介導的組蛋白乙?；{，而組蛋白去乙酰化酶1介導的組蛋白去乙?；撜{Btk轉錄及表達。同時，該研究發現Btk蛋白可以發生乙酰化修飾，Btk蛋白的乙?；赏ㄟ^蛋白激酶Lyn影響Btk蛋白磷酸化。這些結果拓展了對Btk調節及其功能的認識，并有益于對相關疾病的研究。

蛋白乙?；梢阴＾D移酶和去乙?；竸討B調節。進一步的研究發現體內與體外B細胞激活有意義的誘導細胞內乙酰轉移酶活性增加，但是去乙?；富钚圆⒉唤档停@一結果揭示了B細胞激活誘導的（組蛋白和非組蛋白）乙?；侨绾握{節的。這一結果亦有助于研究其他免疫細胞（如T細胞）激活的乙酰化調節。

此外，這項研究還報道了組蛋白去乙?；敢种苿㏕SA誘導Btk mRNA降解。有趣的是，TSA的這一作用并非通過抑制組蛋白去乙酰化酶活性。TSA被廣泛地應用于基礎及臨床研究。已知TSA可導致許多（2-10%）基因的mRNA水平降低，但通常認為TSA是通過對組蛋白去乙?；富钚缘囊种破鹱饔玫?。

Lysine Acetylation Regulates Bruton's Tyrosine Kinase in B Cell Activation

Zhijian Liu,* Antonello Mai, and Jian Sun*

*Laboratory of B-Cell and Autoantibody, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, and ?Shanghai Institute of Immunology, Institutes of Medical Sciences, Shanghai JiaoTong University School of Medicine, Shanghai; Institute of Genetics and Developmental Biology, and Graduate School, Chinese Academy of Sciences, Beijing, China; and Dipartimento di Studi Farmaceutici, Universita degli Studi di Roma La Sapienza, Rome, Italy

Bruton's tyrosine kinase （Btk） is essential for BCR signal transduction and has diverse functions in B cells. Although Btk has been extensively studied, the role of lysine acetylation in Btk regulation has not been reported. In this study, we show that BCR cross-linking induces histone lysine acetylation at the Btk promoter, correlating with marked recruitment of histone acetyltransferase E1A-associated 300-kDa protein （p300） to the locus. These effects enhance Btk promoter activity and increase the expression of Btk mRNA and protein. Consistent with these results, activated B cells display increased p300 expression and total histone acetyltransferase activity in vitro and in vivo, resulting in global histone acetylation. Interestingly, we found that BCR signaling induces Btk lysine acetylation mediated by p300. Moreover, lysine acetylation of Btk promotes its phosphorylation. Together, our results indicate a novel regulatory mechanism for Btk transcription and reveal a previously unrecognized posttranslational modification of the Btk protein and its association with phosphorylation in B cell activation.