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The cis ‐regulatory code of Hox function in Drosophila
Author(s) -
Sorge Sebastian,
Ha Nati,
Polychronidou Maria,
Friedrich Jana,
Bezdan Daniela,
Kaspar Petra,
Schaefer Martin H,
Ossowski Stephan,
Henz Stefan R,
Mundorf Juliane,
Rätzer Jenny,
Papagiannouli Fani,
Lohmann Ingrid
Publication year - 2012
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2012.179
Subject(s) - biology , hox gene , function (biology) , genetics , drosophila (subgenus) , evolutionary biology , computational biology , gene , transcription factor
Precise gene expression is a fundamental aspect of organismal function and depends on the combinatorial interplay of transcription factors (TFs) with cis ‐regulatory DNA elements. While much is known about TF function in general, our understanding of their cell type‐specific activities is still poor. To address how widely expressed transcriptional regulators modulate downstream gene activity with high cellular specificity, we have identified binding regions for the Hox TF Deformed (Dfd) in the Drosophila genome. Our analysis of architectural features within Hox cis ‐regulatory response elements (HREs) shows that HRE structure is essential for cell type‐specific gene expression. We also find that Dfd and Ultrabithorax (Ubx), another Hox TF specifying different morphological traits, interact with non‐overlapping regions in vivo , despite their similar DNA binding preferences. While Dfd and Ubx HREs exhibit comparable design principles, their motif compositions and motif‐pair associations are distinct, explaining the highly selective interaction of these Hox proteins with the regulatory environment. Thus, our results uncover the regulatory code imprinted in Hox enhancers and elucidate the mechanisms underlying functional specificity of TFs in vivo .