GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE330nnn/GSE330120/primaryOK200GenomicsPlasmodium falciparumGenome binding/occupancy profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE330120GEOGSEfalseHMGB proteins modulate chromatin accessibility to coordinate translational capacity in malaria parasites [ATAC-seq_HMGB]Plasmodium falciparum, the causative agent of the most severe form of human malaria, undergoes a complex life cycle that requires rapid adaptation to diverse host environments. This plasticity is largely driven by mechanisms that modulate chromatin structure and gene expression. However, while chromatin dynamics are established regulators of transcriptional control in P. falciparum, their role in regulating expression of the translational machinery is underexplored. Thus, the mechanisms that link chromatin organization to the control of protein synthesis remain poorly defined. Here, we identify two High Mobility Group B proteins, PfHMGB1 and PfHMGB2, as essential chromatin modulators that specifically regulate chromatin accessibility of translation-associated genes. PfHMGB1 and PfHMGB2 co-localize in the nucleus, exhibit highly overlapping interactomes, and bind to similar genome-wide loci. While individual knockdown of either protein had no measurable effect, simultaneous depletion resulted in impaired cell cycle progression, reduced parasite proliferation, and a global decrease in protein synthesis. These phenotypes were coupled with loss of chromatin accessibility in transcribed regions of the translational machinery genes, linking HMGB-dependent chromatin architecture to functional regulation of protein production. Together, our findings establish PfHMGB1 and PfHMGB2 as key regulators of the translational machinery through chromatin-based mechanisms, revealing an underappreciated layer of epigenetic control in malaria parasites.2026/05/13GSE330120GSM9718746GSM9718745GSM9718744GSM9718743GSM9718749GSM9718748GSM9718747GSM9718753GSM9718742GSM9718752GSM9718751GSM971875026836330120Plasmodium falciparum