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Type: Journal article
Title: The bHLH/Per-Arnt-Sim transcription factor SIM2 regulates muscle transcript myomesin2 via a novel, non-canonical E-box sequence
Author: Woods, S.
Farrall, A.
Procko, C.
Whitelaw, M.
Citation: Nucleic Acids Research, 2008; 36(11):3716-3727
Publisher: Oxford Univ Press
Issue Date: 2008
ISSN: 0305-1048
Statement of
Susan Woods, Alexandra Farrall, Carl Procko and Murray L. Whitelaw
Abstract: Despite a growing number of descriptive studies that show Single-minded 2 (Sim2) is not only essential for murine survival, but also upregulated in colon, prostate and pancreatic tumours, there is a lack of direct target genes identified for this basic helix–loop–helix/PAS transcription factor. We have performed a set of microarray experiments aimed at identifying genes that are differentially regulated by SIM2, and successfully verified that the Myomesin2 (Myom2) gene is SIM2-responsive. Although SIM2 has been reported to be a transcription repressor, we find that SIM2 induces transcription of Myom2 and activates the Myom2 promoter sequence when co-expressed with the heterodimeric partner protein, ARNT1, in human embryonic kidney cells. Truncation and mutation of the Myom2 promoter sequence, combined with chromatin immunoprecipitation studies in cells, has lead to the delineation of a non-canonical E-box sequence 5'-AACGTG-3' that is bound by SIM2/ARNT1 heterodimers. Interestingly, in immortalized human myoblasts knock down of Sim2 results in increased levels of Myom2 RNA, suggesting that SIM2 is acting as a repressor in these cells and so its activity is likely to be highly context dependent. This is the first report of a direct SIM2/ARNT1 target gene with accompanying analysis of a functional response element.
Keywords: Kidney
Cell Line
Muscle Proteins
RNA, Messenger
Oligonucleotide Array Sequence Analysis
Gene Expression Profiling
Gene Expression Regulation
RNA Interference
Binding Sites
E-Box Elements
Aryl Hydrocarbon Receptor Nuclear Translocator
Basic Helix-Loop-Helix Transcription Factors
Promoter Regions, Genetic
Transcriptional Activation
DOI: 10.1093/nar/gkn247
Appears in Collections:Aurora harvest
Biochemistry publications

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