Methods and compositions for identifying morphogen analogs

Abstract

Disclosed herein are methods and compositions for identifying morphogen analogs. The preferred methods and compositions relate to the discovery that morphogen upregulation of the mouse type X collagen promoter activity is mediated by a MEF-2 like sequence and requires an adjacent AP-1 sequence. Certain methods rest on the use of test cells comprising DNA defining a morphogen-responsive transcription activating element operatively associated with a reporter gene. Other methods rest on the use of DNAs for measuring morphogen-inducible DNA-binding. In certain preferred embodiments, the methods and DNAs involve an osteogenic protein 1 (OP-1) responsive transcription activating element. Substances that mediate interaction with and/or activate the OP-1 responsive transcription activating element are considered herein likely to be useful for reproducing in vivo effects of morphogens such as OP-1.

1 - 23 . (canceled)  
     
     
         24 . An isolated DNA sequence defining a morphogen-responsive transcription activating element comprising: 
 (a) nucleotides 699-731, 682-731, or 682-761 of SEQ ID NO:1;    (b) species and allelic variants of (a);    (c) DNA which hybridizes to the strand complementary to sequence (a) and is morphogen-responsive under native conditions; and    (d) biosynthetic variants of any of (a), (b), and (c).    
     
     
         25 . The isolated DNA sequence of  claim 24  wherein said morphogen-responsive transcription activating element comprises an MEF-2 binding site sequence adjacent to an AP-1 binding site sequence.  
     
     
         26 - 28 . (canceled)  
     
     
         29 . A cell transfected with the DNA sequence of  claim 24 .  
     
     
         30 - 42 . (canceled)  
     
     
         43 . A cell transfected with the DNA sequence of  claim 25.