Scleraxis

The scleraxis protein is a member of the basic helix-loop-helix (bHLH) superfamily of transcription factors. Currently two genes ( and respectively) have been identified to code for identical scleraxis proteins.

Function
It is thought that early scleraxis expressing progenitor cells lead to the eventual formation of tendon tissue and other muscle attachments. Scleraxis is involved in mesoderm formation and is expressed in the syndetomal (embryonic tissues that develop into tendon and blood vessels) compartment of developing somites (primitive segments or compartments of embryos).

Background
bHLH transcription factors have been shown to have a wide array of functions in developmental processes. More precisely, they have critical roles in the control of cellular differentiation, proliferation and regulation of oncogenesis. To date, 242 eukaryotic proteins belonging to the HLH superfamily have been reported. They have varied expression patterns in all eukaryotes from yeast to humans.

Structurally, bHLH proteins are characterised by a “highly conserved domain containing a stretch of basic amino acids adjacent to two amphipathic α-helices separated by a loop”.

These helices have important functional properties, forming part of the DNA binding and transcription activating domains. With respect to scleraxis, the bHLH region spans amino acid residues 78 to 131. A proline rich region is also predicted to lie between residues 161-170. A stretch of basic residues, which aids in DNA binding, is found closer to the N terminal end of scleraxis.

HLH proteins that lack this basic domain have been shown to negatively regulate the activities of bHLH proteins and are called inhibitors of differentiation (Id). Basic HLH proteins function normally as dimers and bind to a specific hexanucleotide DNA sequence (CAANTG) known as an E-box thus switching on the expression of various genes involved in cellular development and survival.