Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.1.99.3 (PRE)
 1,923 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Proximal regulatory element B (PRE-B), located from positions -318 to -284 in the alpha-myosin heavy chain (MHC) promoter, stimulated expression from an otherwise weak alpha-MHC promoter fragment in primary rat neonatal cardiomyocytes but not in the C2C12 myogenic cell line. PRE-B interacted with alpha-MHC binding factor 2 (BF-2), a protein found in nuclear extracts from several neonatal rat tissues and cell types including cardiomyocytes. BF-2 DNA binding activity was greatly reduced in adult versus neonatal tissues. Methylation interference footprints indicated that BF-2 bound to an element that included an E-box consensus sequence. Site-directed mutations in the BF-2-binding site, that abolish BF-2 binding, reduced expression from the full-length alpha-MHC promoter by 70%. A BF-2-like protein interacts within the HF-1a element of the myosin light chain-2 (MLC-2) promoter suggesting that one of the proteins that regulates the alpha-MHC and MLC-2 genes is identical or closely related. Analysis of binding by competition gel shift experiments indicated that both BF-2 and HF-1a are E-box-binding proteins. The alpha-MHC and MLC-2 genes encode contractile proteins which are precursors of myosin. Regulation by the same transcription factor might indicate that the expression of alpha-MHC and MLC-2 is coordinately controlled.
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PMID:Expression of the alpha-myosin heavy chain gene in the heart is regulated in part by an E-box-dependent mechanism. 842 36