Pınar Önal

Changes in gene expression are among the major causes of phenotypic and morphological differences within and between species as well as between diseased and healthy tissues. In eukaryotes gene expression is regulated at many different levels. Among these is the transcriptional gene regulation, which is mediated by DNA binding proteins called transcription factors. They bind specific DNA sequences called motifs to regulate spatio-temporal gene expression. These motifs are 6-12 bp long and are abundant across the genome. However, a specific transcription factor binds only a subset of potential motifs. How these transcription factors bind right targets among thousands of others at the right time and space is still not fully understood. Drosophila transcription factor Bicoid (Bcd) is a maternal factor which regulates formation of head and thoracic segments. It has a highly conserved and well structured DNA-binding Homeodomain (HD) and transcription activating regions which lack sequence similarity and stable structure under native conditions. These regions are called intrinsically disordered regions (IDRs). While DNA binding HD binds directly to these motifs, IDRs are believed to be involved in different aspects of transcriptional regulation. They might mediate target recognition through promiscuous and weak DNA binding, interact with cofactors, form transcriptional hubs (condensates) and change conformation of the DNA and thereby contribute to transcriptional specificity. We investigate how these different structural regions and mechanisms impact robust and specific transcriptional regulation and development by using in vitro and in vivo techniques in the model of Drosophila embryogenesis.