Lysine acetylation regulates Bruton's tyrosine kinase in B cell activation.
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.
Liu
Zhijian
Z
Laboratory of B-Cell and Autoantibody, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Shanghai JiaoTong University School of Medicine, Shanghai, China.
Mai
Antonello
A
Sun
Jian
J
D000107:Acetylation; D000077329:Agammaglobulinaemia Tyrosine Kinase; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D015153:Blotting, Western; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D005786:Gene Expression Regulation; D006657:Histones / Q000378:metabolism; D008213:Lymphocyte Activation / Q000502:physiology*; D008239:Lysine / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D011499:Protein Processing, Post-Translational; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology*; D014162:Transfection; D050880:p300-CBP Transcription Factors / Q000378:metabolism; D000099224:p300-CBP-Associated Factor
D000077329:Agammaglobulinaemia Tyrosine Kinase; D004791:Enzyme Inhibitors; D006657:Histones; D008239:Lysine; D011505:Protein-Tyrosine Kinases; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C000625951:Btk protein, mouse