The transcriptional cofactor MIER1-beta negatively regulates histone acetyltransferase activity of the CREB-binding protein

被引：17

作者：

Blackmore T.M. ^{[1
]}

Mercer C.F. ^{[1
]}

Paterno G.D. ^{[1
]}

Gillespie L.L. ^{[1
]}

机构：

[1] Terry Fox Cancer Research Laboratories, Division of BioMedical Sciences, Memorial University of Newfoundland, St John's, NL

来源：

BMC Research Notes | / 1卷 / 1期

基金：

加拿大健康研究院;

关键词：

Chromatin Remodel; Histone Acetyltransferase Activity; Histone Binding; Growth Factor Early Response; Sant Domain;

D O I：

10.1186/1756-0500-1-68

中图分类号：

学科分类号：

摘要：

Background: 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, MIER1 and, 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). Findings: 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. Conclusion: Our data indicate that an additional mechanism by which MIER1 could repress transcription involves the inhibition of histone acetyltransferase activity. © 2008 Gillespie et al; licensee BioMed Central Ltd.

引用

共 12 条

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