Folkendt Laura, Lohmann Ingrid, Domsch Katrin
Developmental Biology, Erlangen-Nürnberg University, 91058 Erlangen, Germany.
Centre for Organismal Studies (COS) Heidelberg, Heidelberg University, 69120 Heidelberg, Germany.
J Dev Biol. 2021 Dec 13;9(4):57. doi: 10.3390/jdb9040057.
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 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.
转录因子（TF）网络决定了多细胞生物的精确发育。虽然许多研究聚焦于在特定细胞类型中表达的转录因子，以阐明它们对细胞特化和分化的作用，但对于广泛表达的转录因子如何在不同细胞环境中发挥其精确功能，人们了解较少。为了揭示能够解释此类转录因子组织特异性功能的差异，我们在此利用生物信息学分析了广泛表达的同源异型转录因子超双胸（Ubx）在中胚层和神经组织中的基因组染色质相互作用。我们的研究表明，Ubx优先与这两种组织中基因假定调控区域内多个但具有组织特异性的染色质位点相互作用。重要的是，我们发现经典的同源异型/Ubx DNA结合基序仅在神经元Ubx染色质相互作用中富集，而在中胚层中Ubx结合的区域中鉴定出一种预测与同源异型亲和力相当低的新型Ubx样基序。最后，我们的分析表明，就活性和抑制性组蛋白标记的分布而言，组织特异性Ubx染色质位点也有所不同。基于我们的数据，我们提出，Ubx结合行为的组织相关差异可能是三胚层动物中胚层作为一个新的胚层出现的结果，这可能要求同源异型转录因子放松其结合特异性。
