Cooperative transcriptional activation by serum response factor and the high mobility group protein SSRP1.
Serum response factor (SRF) is a MADS box transcription factor that controls a wide range of genes involved in cell proliferation and differentiation. The MADS box mediates homodimerization and binding of SRF to the consensus sequence CC(A/T)6GG, known as a CArG box, which is found in the control regions of numerous serum-inducible and muscle-specific genes. Using a modified yeast one-hybrid screen to identify potential SRF cofactors, we found that SRF interacts with the high mobility group factor SSRP1 (structure-specific recognition protein). This interaction, which occurs in yeast and mammalian cells, is mediated through the MADS box of SRF and a basic region of SSRP1 encompassing amino acids 489-542, immediately adjacent to the high mobility group domain. SSRP1 does not bind the CArG box, but interaction of SSRP1 with SRF dramatically increases the DNA binding activity of SRF, resulting in synergistic transcriptional activation of native and artificial SRF-dependent promoters. These results reveal an important role for SSRP1 as a coregulator of SRF-dependent transcription in mammalian cells.
Spencer
J A
JA
Department of Molecular Biology and Oncology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75235-9148, USA.
Baron
M H
MH
Olson
E N
EN
D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000494:pharmacology*; D005786:Gene Expression Regulation; D006609:High Mobility Group Proteins / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism / Q000494:pharmacology*; D026362:Serum Response Factor; D014157:Transcription Factors / Q000494:pharmacology; D015533:Transcriptional Activation; D015003:Yeasts / Q000235:genetics
D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D009687:Nuclear Proteins; D026362:Serum Response Factor; D014157:Transcription Factors