Abstract
Transcription factor (TF) networks define the precise development of multicellular organisms. While many studies focused on TFs expressed in specific cell types to elucidate their contribution to cell specification and differentiation, it is less understood how broadly expressed TFs perform their precise functions in the different cellular contexts. To uncover differences that could explain tissue-specific functions of such TFs, we analyzed here genomic chromatin interactions of the broadly expressed Drosophila Hox TF Ultrabithorax (Ubx) in the mesodermal and neuronal tissues using bioinformatics. Our investigations showed that Ubx preferentially interacts with multiple yet tissue-specific chromatin sites in putative regulatory regions of genes in both tissues. Importantly, we found the classical Hox/Ubx DNA binding motif to be enriched only among the neuronal Ubx chromatin interactions, whereas a novel Ubx-like motif with rather low predicted Hox affinities was identified among the regions bound by Ubx in the mesoderm. Finally, our analysis revealed that tissues-specific Ubx chromatin sites are also different with regards to the distribution of active and repressive histone marks. Based on our data, we propose that the tissue-related differences in Ubx binding behavior could be a result of the emergence of the mesoderm as a new germ layer in triploblastic animals, which might have required the Hox TFs to relax their binding specificity.
Highlights
The development of multicellular organisms is coordinated by distinct sets of transcription factors (TFs) that work in networks to initiate cell fate decision, specification, cell localization and tissue differentiation [1,2,3]
One possibility is that Hox proteins bind different and more specific sequences in different cellular contexts; so far, binding preferences of Hox proteins in different cell or tissue types have not been studied in a systematic fashion
The evolutionary conserved Hox proteins perform very specific functions in vivo; in vitro, they bind rather generic and frequently occurring DNA sequences. This raises two important questions related to Hox specificity: first, how do different Hox proteins control segment-specific features, and second, how does a single Hox protein regulate the development of different cell and tissue types present in one segment in a specific manner
Summary
The development of multicellular organisms is coordinated by distinct sets of transcription factors (TFs) that work in networks to initiate cell fate decision, specification, cell localization and tissue differentiation [1,2,3]. Hox genes are evolutionary conserved and specify the segment identity along the anterior-posterior axis of the developing embryo [8,9,10,11]. They are required in the different cell and tissue types of a defined segment. Despite their highly specific function in vivo, Hox proteins are characterized by a rather unspecific binding behavior in vitro, a phenomenon known as the Hox paradox [12,13,14]. This paradox has been intensively investigated, which resulted in deep insights from in vitro experiments enriching for DNA sequences with which Hox proteins (and their cofactors) interact [15], or from in vivo studies testing the binding abilities of different Hox proteins to selected
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