Abstract
BackgroundSmoothelin-like 1 (SMTNL1, also known as CHASM) plays a role in promoting relaxation as well as adaptive responses to exercise, pregnancy and sexual development in smooth and skeletal muscle. Investigations of Smtnl1 transcriptional regulation are still lacking. Thus, in this study, we identify and characterize key regulatory elements of the mouse Smtnl1 gene.ResultsWe mapped the key regulatory elements of the Smtnl1 promoter region: the transcriptional start site (TSS) lays -44 bp from the translational start codon and a TATA-box motif at -75 bp was conserved amongst all mammalian Smtnl1 promoters investigated. The Smtnl1 proximal promoter enhances expression up to 8-fold in smooth muscle cells and a second activating region lays 500 bp further upstream. Two repressing motifs were present (-118 to -218 bp and -1637 to -1869 bp). The proximal promoter is highly conserved in mammals and contains a mirror repeat sequence. In silico analysis suggests many transcription factors (notably MyoD) could potentially bind within the Smtnl1 proximal promoter sequence.ConclusionSmtnl1 transcript was identified in all smooth muscle tissues examined to date, albeit at much lower levels than found in skeletal muscle. It is unlikely that multiple SMTNL1 isoforms exist since a single Smtnl1 transcription start site was identified in both skeletal and intestinal smooth muscle. Promoter studies suggest restrictive control of Smtnl1 expression in non-muscle cells.
Highlights
Smoothelin-like 1 (SMTNL1, known as calponin homology-associated smooth muscle protein (CHASM)) plays a role in promoting relaxation as well as adaptive responses to exercise, pregnancy and sexual development in smooth and skeletal muscle
SMTNL1 is closely related to the smoothelin family of proteins (SMTN) that are used as markers for contractile smooth muscle cell differentiation [7,8]
Given that SMTNL1 is expressed in multiple muscle types, it was expected that Smtnl1 transcriptional regulation might differ from the other smoothelin family members
Summary
Smoothelin-like 1 (SMTNL1, known as CHASM) plays a role in promoting relaxation as well as adaptive responses to exercise, pregnancy and sexual development in smooth and skeletal muscle. Experiments completed in situ with isolated smooth muscle tissues suggest a physiological role for SMTNL1 in promoting the relaxant actions of PKA/PKG [1,2], and studies with Smtnl genetic knock-out mice link SMTNL1 with adaptive responses to exercise in both smooth and skeletal muscle [3]. SRF and myocardin play critical roles in the expression and regulation of growth-responsive genes as well as the expression of virtually all smooth muscle specific genes, such as calponin, myosin heavy chain, a-actin and SM-22 [13,14]. Given that SMTNL1 is expressed in multiple muscle types, it was expected that Smtnl transcriptional regulation might differ from the other smoothelin family members
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