Repression of transcription by TSGA/Jmjd1a, a novel interaction partner of the ETS protein ER71.
Testis-specific gene A (TSGA) was originally identified in rat and shown to be expressed within the testes. Here, we have cloned the murine homolog [also known as jumonji domain-containing 1a (Jmjd1a)] and for the first time characterized the TSGA protein and its functions. Although murine TSGA is expressed in testes, its mRNA is also present in many other tissues, including heart, thymus, liver, and skin. Immunostaining revealed that TSGA is a nuclear protein, whose N-terminus contains a putative nuclear localization signal. TSGA displays significant homology to a suspected tumor suppressor and coactivator (5qNCA), to a thyroid hormone receptor interacting protein (TRIP8) and to the corepressor Hairless, pointing at a role of TSGA in transcription regulation. Indeed, TSGA contains several functional transcription repression domains. In addition, TSGA interacts both in vitro and in vivo with ER71 (ETS related 71), a transcription factor that is expressed in the testes of adult mice and during embryogenesis. Specifically, the N-terminus of TSGA and the C-terminus of ER71 are primarily engaged in their complex formation. Furthermore, TSGA impairs the ability of ER71 to activate transcription from the matrix metalloproteinase-1 promoter. Thus, TSGA may modulate the function of ER71 and thereby affect spermatogenesis as well as embryonic development.
Knebel
Julia
J
Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, Minnesota 55905, USA.
De Haro
Luciano
L
Janknecht
Ralf
R
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D056466:Histone Demethylases; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism*; D010089:Oxidoreductases, N-Demethylating; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; C503994:ER71 protein, mouse; D009687:Nuclear Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D056466:Histone Demethylases; D056484:Jumonji Domain-Containing Histone Demethylases; C511045:Kdm3a protein, mouse; D010089:Oxidoreductases, N-Demethylating; D020781:Matrix Metalloproteinase 1; C000624330:histone demethylase KDM3a, rat