Expression and function of Set7/9 in pancreatic islets.
Expression and function of Set7/9 in pancreatic islets.
复制标题
DOI：
10.4161/isl.1.3.9779
复制
发表时间：
2009-11
期刊：
影响因子：
2.2
通讯作者：
Mirmira RG
中科院分区：
文献类型：
--
作者：
Ogihara T;Vanderford NL;Maier B;Stein RW;Mirmira RG
已知组蛋白尾部乙酰化和甲基化增强胰岛基因对转录因子和基础转录机制的可及性。在这份简短的报告中，我们跟进了最近的一项研究，其中我们鉴定了胰岛富集因子Set 7/9作为β细胞中潜在重要的组蛋白甲基转移酶（Deering等人，Diabetes 2009; 58：185-93）。我们认为Set 7/9对H3-Lys 4的甲基化增强了胰岛素基因对基础转录机制的可及性。与这一假设相一致，我们在此表明，与α细胞（或NIH 3 T3细胞）相比，β细胞中胰岛素和IAPP基因的RNA聚合酶II占有率显著增强，而胰高血糖素基因的RNA聚合酶II占有率则匡威。β细胞中Set 7/9的富集似乎依赖于Pdx 1，因为使用小发夹RNA敲低INS-1 β细胞中的Pdx 1几乎完全消除Set 7/9表达。由含有推定的Pdx 1结合位点的-6.5内切酶对Set 7/9启动子驱动的LacZ表达载体显示β细胞系特异性表达。综上所述，我们的数据进一步支持了Pdx 1依赖性Set 7/9表达可能对增强染色质可及性和β细胞基因转录至关重要的假设。
Histone tail acetylation and methylation are known to enhance accessibility of islet genes to transcription factors and the basal transcriptional machinery. In this brief report, we follow up on a recent study in which we identified the islet enriched factor Set7/9 as a potentially important histone methyltransferase in β cells (Deering, et al. Diabetes 2009; 58:185-93). We had suggested that the methylation of H3-Lys4 by Set7/9 enhances accessibility of the insulin gene to the basal transcriptional machinery. Consistent with this hypothesis, we show here that RNA polymerase II occupancy at the insulin and IAPP genes is considerably enhanced in β cells compared to α cells (or NIH3T3 cells), and that the converse is true for RNA polymerase II occupancy at the glucagon gene. The enrichment of Set7/9 in β cells appears to be dependent upon Pdx1, as knockdown of Pdx1 in INS-1 β cells using small hairpin RNAs almost completely abolishes Set7/9 expression. A LacZ expression vector driven by the -6.5 kilobase pair Set7/9 promoter that contains putative Pdx1 binding sites shows β cell-line-specific expression. Taken together, our data support further the hypothesis that Pdx1-dependent Set7/9 expression may be crucial to enhancing chromatin accessibility and transcription of β cell genes.
登录
查看更多内容
影响因子：
4.8
作者：
Chakrabarti, SK;James, JC;Mirmira, RG
通讯作者：
Mirmira, RG
DOI：
10.1073/pnas.182436399
发表时间：
2002-12-10
影响因子：
11.1
作者：
Noma, K;Grewal, SIS
通讯作者：
Grewal, SIS
影响因子：
4.8
作者：
Francis, J;Chakrabarti, SK;Mirmira, RG
通讯作者：
Mirmira, RG
影响因子：
4.8
作者：
Iype, T;Francis, J;Mirmira, RG
通讯作者：
Mirmira, RG
影响因子：
56.9
作者：
Noma, K;Allis, CD;Grewal, SIS
通讯作者：
Grewal, SIS