Blackmore, Tina M. and Mercer, Corinne F. and Paterno, Gary D. and Gillespie, Laura L. (2008) The transcriptional cofactor MIER1-beta negatively regulates histone acetyltransferase activity of the CREB-binding protein. BMC Research Notes, 1 (68). pp. 1-5. ISSN 1756-0500
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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.
|Department(s):||Medicine, Faculty of > Biomedical Sciences|
|Date:||21 August 2008|
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