アクティブボード・2013年 8月
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研究発表を行った学会;
・第41回日本免疫学会学術集会
 2012年12月 5日〜 7日(神戸)

タイトル;GANP regulates transcription and nucleosome occupancy at the immunoglobulin variable region for AID-accession.
発表者;前田 和彦 氏
   (熊本大学 大学院生命科学研究部 免疫学分野)
Abstract;
Antigen-driven B-cells undergo immunoglobulin (Ig) variable (V)-region somatic hypermutation (SHM) by inducing activation-induced cytidine deaminase (AID). We have shown that AID is recruited to the IgV-region locus by the help of germinal center-associated nuclear protein (GANP) in B-cells. Here, we investigate how GANP regulates nucleosome occupancy for AID-accession to the rearranged IgV-region locus. GANP enhances acetylation of lysines in histone H3 and H1 at the VDJ-rearranged IgV-locus through the C-terminal GANP region possessing histone acetyltransferase (HAT) activity. GANP interacts to the particular two positions that clip the rearranged IgV-region at both the 5’- and 3’-ends similarly to RNA polymerase II (Pol-II) stall factors. These positions are usually nuclease resistant but the 3’-end of the rearranged IgV-region becomes sensitive to Micrococcal nuclease by GANP, suggesting that GANP unlocks the nucleosome by the acetylation of the linker histone H1 at the 3’-side end in B-cells. Chromatin-bound GANP modulates nucleosome occupancy for AID positioning at the IgV-locus by interacting with the transcription complex, resulting in the increase of the AID-mediated IgV-region SHM. GANP promotes the transcriptional activation by modifying the epigenetic status of IgV-region as the SHM factory.