Cooperation or Competition? Unraveling the interplay between transcription and epigenetic factors in Toxoplasma gondii gene expression

Regulation of gene expression in Toxoplasma gondii is mediated by a complex interplay between ApiAP2 transcription factors (TFs), chromatin remodelers, and protein complexes. Although this interplay has been experimentally interrogated (e.g., MORC/HDAC3 complex), the degree of these interactions and the universality of this mechanism has not been examined. Here, we present a comprehensive dissection of all publicly available as well as newly generated chromatin immunoprecipitation data (ChIP-chip, ChIP-seq, CUT&RUN, and CUT&TAG) performed on multiple TFs and epigenetic factors (EFs) in Toxoplasma gondii. Analysis of the data revealed that several TFs and EFs have overlapping binding loci and common motifs across the genome, hinting at the existence of core complex(es) that operate cooperatively or competitively to regulate gene expression and developmental programs. We developed a Hidden Markov Model (HMM) that segments the genome based on chromatin engagement signatures by various factors into distinct states that correlate with gene expression patterns. Overall, our analysis reveals that there may be universal mechanisms involving core complexes of TFs and EFs that regulate gene expression in T. gondii.