When ETS transcription factors meet their partners

CNRS UMR 8526, Institut de Biologie de Lille, B.P. 447, 1 rue Calmette, 59021 Lille Cedex, France.
BioEssays (Impact Factor: 4.73). 04/2002; 24(4):362-70. DOI: 10.1002/bies.10068
Source: PubMed


Ets proteins are a family of transcription factors that regulate the expression of a myriad of genes in a variety of tissues and cell types. This functional versatility emerges from their interactions with other structurally unrelated transcription factors. Indeed, combinatorial control is a characteristic property of Ets family members, involving interactions between Ets and other key transcriptional factors such as AP1, SRF, and Pax family members. Intriguingly, recent molecular modeling and crystallographic data suggest that not only the ETS DNA-binding domain, but also the DNA recognition helix alpha3, are often directly required for Ets partner's selection. Indeed, while most DNA-binding proteins appear to exploit differences within their DNA recognition helices for sites selection, the Ets proteins exploit differences in their surfaces that interact with other transcription factors, which in turn may modify their DNA-binding properties in a promoter-specific fashion. Taken together, the gene-specific architecture of these unique complexes can mediate the selective control of transcriptional activity.

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    • "However, the percentage for ELK4 association with SRF peaks was relatively lower (44.7%, 350 out of 783), indicating that ELK4 may have other functions independent of SRF and could have other co-regulators [37]. "
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    • "Transcripts in gene network A (Supplementary Material, Table S7) included multiple genes associated with autoimmune diseases (Cd6, Ets1, Tcf7 and Themis) (2, 36–38). The Cd6 MS susceptibility allele is associated with alterations in T cell proliferation (39) and the transcription factor Ets1 participates in important aspects of early thymocyte development (40, 41). Several genes, including Lef1, Lck, Crtam and Itk, have previously been linked to functions of the adaptive immune system. "
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    • "The demonstration that ETS-family TFs have distinct functions (9) even though they share the same DNA recognition motifs raised an important question about what determines the specificity of TF-mediated transcriptional activity. The expression pattern of the ETS factors and the tissue-specific expression of cooperating factors (6,10) contribute to this specificity. It has been shown that distinct cooperative partnership dictates the specificity of the transcriptional regulation by two different ETS TFs, ETS1 and GABPα, expressed in the same cell type (11,12). "
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