The transcriptional cofactor MIER1-beta negatively regulates histone acetyltransferase activity of the CREB-binding protein.
The transcriptional cofactor MIER1-beta negatively regulates histone acetyltransferase activity of the CREB-binding protein.
复制标题
转录辅因子MIER1-β对CREB结合蛋白的组蛋白乙酰转移酶活性负调节。
DOI：
10.1186/1756-0500-1-68
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发表时间：
2008-08-22
影响因子：
1.8
通讯作者：
Gillespie LL
中科院分区：
文献类型：
--
作者：
Blackmore TM;Mercer CF;Paterno GD;Gillespie LL
Mier 1编码一种新的转录调节因子，最初是作为成纤维细胞生长因子早期反应基因分离的。已经鉴定了两种主要的蛋白质同种型，MIER 1 α和β，它们的C-末端序列不同。以前，我们证明了这两种亚型招募组蛋白脱乙酰酶1（HDAC 1）抑制转录。为了进一步探讨MIER 1在染色质重塑中的作用，我们研究了MIER 1与组蛋白乙酰转移酶（HAT）、Creb结合蛋白（CBP）的功能相互作用。使用GST下拉分析，我们证明了MIER 1与CBP相互作用，并且这种相互作用涉及MIER 1的N-末端一半（氨基酸1-283），其包括酸性激活和ELM 2结构域和CBP的C-末端一半（氨基酸1094-2441），其包括溴，HAT，C/H3和谷氨酰胺丰富的结构域。使用HEK 293细胞进行的功能分析显示，与MIER 1结合的CBP在体内没有可检测到的HAT活性。组蛋白4肽结合试验表明，这种HAT活性的抑制不是干扰组蛋白结合的结果。我们的数据表明，MIER 1可以抑制转录的另一种机制涉及抑制组蛋白乙酰转移酶活性。
Mier1 encodes a novel transcriptional regulator and was originally isolated as a fibroblast growth factor early response gene. Two major protein isoforms have been identified, MIER1α and β, which differ in their C-terminal sequence. Previously, we demonstrated that both isoforms recruit histone deacetylase 1 (HDAC1) to repress transcription. To further explore the role of MIER1 in chromatin remodeling, we investigated the functional interaction of MIER1 with the histone acetyltransferase (HAT), Creb-binding protein (CBP). Using GST pull-down assays, we demonstrate that MIER1 interacts with CBP and that this interaction involves the N-terminal half (amino acids 1–283) of MIER1, which includes the acidic activation and ELM2 domains and the C-terminal half (amino acids 1094–2441) of CBP, which includes the bromo-, HAT, C/H3 and glutamine-rich domains. Functional analysis, using HEK293 cells, shows that the CBP bound to MIER1 in vivo has no detectable HAT activity. Histone 4 peptide binding assays demonstrate that this inhibition of HAT activity is not the result of interference with histone binding. Our data indicate that an additional mechanism by which MIER1 could repress transcription involves the inhibition of histone acetyltransferase activity.