The transcriptional cofactor MIER1-beta negatively regulates histone acetyltransferase activity of the CREB-binding protein.
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, MIER1alpha and beta, 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).


RESULTS
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.


CONCLUSIONS
Our data indicate that an additional mechanism by which MIER1 could repress transcription involves the inhibition of histone acetyltransferase activity.
Blackmore
Tina M
TM
Terry Fox Cancer Research Laboratories, Division of BioMedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St John's, NL, A1B 3V6, Canada. tinablackmore@mun.ca
Mercer
Corinne F
CF
Paterno
Gary D
GD
Gillespie
Laura L
LL