Brown Alan S, Llinás Manuel, Mahony Shaun
Center for Eukaryotic Gene Regulation, Department of Biochemistry & Molecular Biology, The Pennsylvania State University, PA 16802.
Huck Center for Malaria Research, The Pennsylvania State University, PA 16802.
bioRxiv. 2025 Aug 28:2025.08.22.671872. doi: 10.1101/2025.08.22.671872.
The interdependence of chromatin states and transcription factor (TF) binding in eukaryotic genomes is critical for the proper regulation of gene expression. In this study, we explore the connection between TFs and chromatin states in the human malaria parasite, , throughout its 48-hour asexual intraerythrocytic developmental cycle (IDC). Most genes are expressed in a periodic manner during the IDC, accompanied by dynamic shifts in histone modifications and chromatin accessibility. Leveraging genome-wide profiles of chromatin accessibility, histone modifications, and Heterochromatin Protein 1 (HP1) occupancy, we characterize chromatin state dynamics during the IDC. Our results indicate that several chromatin states remain stable throughout the lifecycle, while others are dynamic and are linked to gene activation or repression. We further characterize chromatin state dynamics at the genome-wide DNA binding sites for a selection of TFs, allowing us to group TFs according to their chromatin preferences. By correlating changes in chromatin accessibility, histone modifications, and TF binding, we provide a global overview of the chromatin state dynamics that coordinate asexual blood stage development.
染色质状态与真核生物基因组中转录因子(TF)结合之间的相互依存关系对于基因表达的正确调控至关重要。在本研究中,我们探究了人类疟原虫在其48小时无性红细胞内发育周期(IDC)中TFs与染色质状态之间的联系。大多数基因在IDC期间以周期性方式表达,同时伴随着组蛋白修饰和染色质可及性的动态变化。利用染色质可及性、组蛋白修饰和异染色质蛋白1(HP1)占据情况的全基因组图谱,我们描绘了IDC期间的染色质状态动态变化。我们的结果表明,几种染色质状态在整个生命周期中保持稳定,而其他状态则是动态的,并且与基因激活或抑制相关。我们进一步描绘了一组选定TFs在全基因组DNA结合位点处的染色质状态动态变化,这使我们能够根据它们的染色质偏好对TFs进行分组。通过关联染色质可及性、组蛋白修饰和TF结合的变化,我们提供了协调无性血液阶段发育的染色质状态动态变化的全局概述。