Borders of Cis -Regulatory DNA Sequences Preferentially Harbor the Divergent Transcription Factor Binding Motifs in the Human Genome

• Published in: Frontiers in genetics 2018-11, Vol.9, p.571-571
• Main Authors: Huang, Jia-Hsin, Kwan, Ryan Shun-Yuen, Tsai, Zing Tsung-Yeh, Lin, Tzu-Chieh, Tsai, Huai-Kuang
• Format: Article
• Language: English
• Subjects: cis-regulatory elements; Genetics; motifs; open chromatins; TF binding specificities; transcription factor binding sites
• ISSN: 1664-8021; 1664-8021
• DOI: 10.3389/fgene.2018.00571

Changes in -regulatory DNA sequences and transcription factor (TF) repertoires provide major sources of phenotypic diversity that shape the evolution of gene regulation in eukaryotes. The DNA-binding specificities of TFs may be diversified or produce new variants in different eukaryotic species. However, it is currently unclear how various levels of divergence in TF DNA-binding specificities or motifs became introduced into the -regulatory DNA regions of the genome over evolutionary time. Here, we first estimated the evolutionary divergence levels of TF binding motifs and quantified their occurrence at DNase I-hypersensitive sites. Results from our motif scan and experimentally derived chromatin immunoprecipitation (TF-ChIP) show that the divergent motifs tend to be introduced in the edges of -regulatory regions, which is probably accompanied by the expansion of the accessible core of promoter-associated regulatory elements during evolution. We also find that the genes neighboring the expanded -regulatory regions with the most divergent motifs are associated with functions like development and morphogenesis. Accordingly, we propose that the accumulation of divergent motifs in the edges of -regulatory regions provides a functional mechanism for the evolution of divergent regulatory circuits.