DNA sequence context and the chromatin landscape differentiate sequence-specific transcription factor binding in the human malaria parasite, Plasmodium falciparum

ABSTRACT: Global transcription of the malaria parasite, Plasmodium falciparum, is finely regulated, yet the genome encodes for a limited number of sequence-specific transcription factors (TFs) to coordinate this pattern. A subset of these TFs bind overlapping DNA motifs (i.e., CACACA and GTGCAC); however, mechanisms of binding site selection and redundancy have not yet been investigated in P. falciparum. Therefore, we integrated a variety of approaches from new and published work such as high-throughput in vitro and in vivo binding assays, DNA shape predictions, epigenetic post translational modification mapping, and genome-wide chromatin accessibility mapping to comprehensively interrogate the impact of DNA sequence context and the chromatin landscape on TF binding in P. falciparum. We show that sequence context of the CACACA-binding TFs does not greatly impact binding site selection, while chromatin accessibility, epigenetic patterns, and co-factor recruitment differentiates in vivo binding. In contrast, the GTGCAC-binding TFs do prefer significantly different sequence contexts and DNA shape profiles both in vitro and in vivo, in concert with chromatin dynamics. Our results demonstrate that TFs select binding sites based on unique combinations of sequence context, DNA topology, epigenetic patterns, and chromatin accessibility, thereby contributing to the complex gene regulatory mechanisms governing malaria pathogenesis.

ORGANISM(S): Plasmodium falciparum

PROVIDER: GSE212052 | GEO | 2024/07/31

REPOSITORIES: GEO