Zinc Finger Independent Genome-Wide Binding of Sp2 Potentiates Recruitment of Histone-Fold Protein Nf-y Distinguishing It from Sp1 and Sp3


A major question in eukaryotic gene regulation is how transcription factors with similar structural features elicit specific biological responses. We used the three transcription factors Sp1, Sp2 and Sp3 as a paradigm for investigating this question. All three proteins are ubiquitously expressed, and they share glutamine-rich domains as well as a conserved bona fide zinc finger DNA binding domain. Yet, each of the three proteins carries out unique functions in vivo, and each is absolutely essential for mouse development. By genome-wide binding analysis, we found that Sp1 and Sp3 on the one hand, and Sp2 on the other hand engage completely different protein domains for their genomic binding site selection. Most strikingly, the zinc finger domain of Sp2 is dispensable for recruitment to its target sites in vivo. Moreover, we provide strong evidence that the histone-fold protein Nf-y is necessary for recruitment of Sp2. Conversely, Sp2 potentiates Nf-y binding showing that binding of Sp2 and Nf-y to shared sites is mutually dependent. Our findings uncover an unexpected mechanistic diversity in promoter recognition by seemingly similar transcription factors. This work has broader implications for our understanding of how members of other multi-protein transcription factor families could achieve specificity.


Vyšlo v časopise: Zinc Finger Independent Genome-Wide Binding of Sp2 Potentiates Recruitment of Histone-Fold Protein Nf-y Distinguishing It from Sp1 and Sp3. PLoS Genet 11(3): e32767. doi:10.1371/journal.pgen.1005102
Kategorie: Research Article
prolekare.web.journal.doi_sk: 10.1371/journal.pgen.1005102

Souhrn

A major question in eukaryotic gene regulation is how transcription factors with similar structural features elicit specific biological responses. We used the three transcription factors Sp1, Sp2 and Sp3 as a paradigm for investigating this question. All three proteins are ubiquitously expressed, and they share glutamine-rich domains as well as a conserved bona fide zinc finger DNA binding domain. Yet, each of the three proteins carries out unique functions in vivo, and each is absolutely essential for mouse development. By genome-wide binding analysis, we found that Sp1 and Sp3 on the one hand, and Sp2 on the other hand engage completely different protein domains for their genomic binding site selection. Most strikingly, the zinc finger domain of Sp2 is dispensable for recruitment to its target sites in vivo. Moreover, we provide strong evidence that the histone-fold protein Nf-y is necessary for recruitment of Sp2. Conversely, Sp2 potentiates Nf-y binding showing that binding of Sp2 and Nf-y to shared sites is mutually dependent. Our findings uncover an unexpected mechanistic diversity in promoter recognition by seemingly similar transcription factors. This work has broader implications for our understanding of how members of other multi-protein transcription factor families could achieve specificity.


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