ALF1, a basic helix-loop-helix transcription factor, maps to mouse chromosome 9

Species: Mouse. Locus description: A gene coding for a transcription factor with a basic helix-loop-helix domain. Locus symbol: Tcf12. Method of mapping: Southern blot analysis of BXD RI strains. Molecular reagents: A 1.6-kb EcoRI-NotI ALF1 cDNA fragment inserted in pBluescript was radiolabeled and used in Southern blotting experiments as described. DNA from 26 BXD RI strains were from The Jackson Laboratory. Discussion: Transcription factors with a DNA binding domain of the basic helix-loop-helix (bHLH) type is a rapidly growing family of proteins. The mouse ALF1 protein is a bHLH transcription factor mediating transcriptional trans-activation through the E-box DNA motif, CAGNTG. Human and rat ALF1 analogs are abbreviated HEB/HTF4 and REB respectively. The ALF1 protein belongs to a subfamily of bHLH proteins including E2-2 and the products from the E2A gene, E2-5, E12, and E47. By the usage of alternative splicing, ALF1 mRNA exists in two forms having variable expression levels dependent on tissue type. Southern blot analyses indicates that the ALF1 gene, Tcf12, has multiple large introns and is sized approximately 150 kb. For mapping the position of Tcf12 in the mouse genome, we used Southern blotting to search for restriction fragment length polymorphism in the BXD RI mouse strains. Polymorphism was observed with complete EcoRI digestion. A single polymorphic band with the size of 4.3 kb was detected in the DBA/2J strain. This band was absent in the C57BL/6J strain, where increased intensity of a 4.0-kb band was observed. Moreover, a group of conserved bands were observed between the C57BL/6J and DBA/2J strains. The probe corresponding to the Tcf12 gene did not cross-hybridize with the very homologous E2A gene, indicating that the multiplicity of observed bands represents Tcf12 specific bands (data not shown). The polymorphism in the Tcf12 gene allowed us to derive a strain distribution pattern (SDP) for the BXD strains.