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An ISWI-related chromatin remodeler orchestrates parasite lifecycle progression by insulating gene expression in a densely packed genome [ATAC-seq]

ABSTRACT: In eukaryotic cells, ATP-dependent chromatin remodelers are specialized multiprotein machines that organize the genome and rule its accessibility by repositioning, ejecting or modifying nucleosomes, but their role in Toxoplasma gondii is still poorly understood. Phylogenetic analyzes show that the parasite retains the four commonly recognized remodeler families and has evolved two divergent proteins within the ISWI family: TgSNF2h and TgSNF2L. These proteins are structurally divergent and form distinct complexes. TgSNF2h specifically forms a core complex with the transcription factor AP2VIII-2 and the scaffold protein TgRFTS. Depletion of TgRFTS phenocopies the knockdown of TgSNF2h, restricting access to chromatin and altering local gene expression. At the genomic level, TgSNF2h actively insulates highly transcribed genes from their minimally expressed or silenced neighbors. This ISWI complex establishes and maintains stage-specific gene expression by regulating the chromatin accessibility to transcription factors. Using MORC as a proxy, we have shown that TgSNF2h rules DNA accessibility and thereby exerts an epistatic control over a key regulator of sexual commitment. In a parasite characterized by high phenotypic plasticity and a compact genome, this dedicated ISWI complex orchestrates the partitioning of developmental genes and ensures transcriptional fidelity throughout its life cycle.

ORGANISM(S): Toxoplasma gondii

PROVIDER: GSE271901 | GEO | 2025/02/19

REPOSITORIES: GEO

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Project description:In eukaryotic cells, ATP-dependent chromatin remodelers are specialized multiprotein machines that organize the genome and rule its accessibility by repositioning, ejecting or modifying nucleosomes, but their role in Toxoplasma gondii is still poorly understood. Phylogenetic analyzes show that the parasite retains the four commonly recognized remodeler families and has evolved two divergent proteins within the ISWI family: TgSNF2h and TgSNF2L. These proteins are structurally divergent and form distinct complexes. TgSNF2h specifically forms a core complex with the transcription factor AP2VIII-2 and the scaffold protein TgRFTS. Depletion of TgRFTS phenocopies the knockdown of TgSNF2h, restricting access to chromatin and altering local gene expression. At the genomic level, TgSNF2h actively insulates highly transcribed genes from their minimally expressed or silenced neighbors. This ISWI complex establishes and maintains stage-specific gene expression by regulating the chromatin accessibility to transcription factors. Using MORC as a proxy, we have shown that TgSNF2h rules DNA accessibility and thereby exerts an epistatic control over a key regulator of sexual commitment. In a parasite characterized by high phenotypic plasticity and a compact genome, this dedicated ISWI complex orchestrates the partitioning of developmental genes and ensures transcriptional fidelity throughout its life cycle.

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Project description:An ISWI-related chromatin remodeler orchestrates parasite lifecycle progression by insulating gene expression in a densely packed genome [RNA-seq]

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Expansion of the ISWI chromatin remodeler family with new active complexes

Project description:ISWI chromatin remodelers mobilize nucleosomes to control DNA accessibility. Complexes isolated to date pair one of six regulatory subunits with one of two highly similar ATPases. However, we find that each endogenously expressed ATPase copurifies with every regulatory subunit, substantially increasing the diversity of ISWI complexes, and we additionally identify BAZ2B as a novel, seventh regulatory subunit. Through reconstitution of catalytically active human ISWI complexes, we demonstrate that the new interactions described here are stable and direct. Finally, we profile the nucleosome remodeling functions of the now expanded family of ISWI chromatin remodelers. By revealing the combinatorial nature of ISWI complexes, we provide a basis for better understanding ISWI function in normal settings and disease.

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Systematic assessment of ISWI subunits reveals that NURF creates local accessibility for proper CTCF function

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Snf2L drives Plasmodium just-in-time gene expression and gametocytogenesis

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