SRF AND TEF-1 CONTROL OF CHICKEN SKELETAL ALPHA-ACTIN GENE DURING SLOW-MUSCLE HYPERTROPHY

The purpose of this study was to delineate the alpha-actin regulatory elements and transcription factors that are responsible for conferring stretch-overload responsiveness during hypertrophy of the anterior la tissimus dorsi (ALD) muscle of young chickens by weighting one wing. M inimal promoter constructs were evaluated by direct injection into the ALD, which demonstrated that both serum response element 1 (SRE1) and the transcriptional enhancer factor 1 (TEF-1) elements were sufficien t for increased expression during stretch overload. A mutated SRE1 pre vented expression in both basal and stretched ALD muscles, whereas a m utated TEF-1 element-reduced actin promoter function in both control a nd stretched muscles. The serum response factor (SRF)-SRE1 binding com plex demonstrated faster migration in mobility shift assays from day 3 - and day 6-stretched ALD nuclear extracts relative to their control. TEF-1 binding was qualitatively increased in stretched extracts at day 3 but not day 6 of stretch overload. Skeletal alpha-actin mRNA accumu lated from day 3 to day 6 of stretch overload. These data demonstrate that SRE1 is necessary and sufficient for stretch-overload responsiven ess from the skeletal alpha-actin promoter and that the SRF-SRE1 bindi ng complex migrates faster in stretched nuclear extracts of hypertroph ied relative to control extracts from intact ALD muscles of chickens.