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Peer-reviewedCC BY-NC-NDNature communications

A SAGA-like AP2-P-ARP1-GCN5 transcriptional complex targets pathogenesis-associated genes during the blood-stage development of Babesia gibsoni.

  • Zhen Han1,2
  • Yaxin Zheng1,2
  • Wei Liu1,2
  • Wanxin Luo1,2
  • Chenglong Wu1,2
  • Jianyu Wang1,2
  • Fangwei Chen1,2
  • Lan He3,4,5,6
  • Junlong Zhao7,8,9
9 affiliations
  1. 1National Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, 430070, China.
  2. 2Key Laboratory of Preventive Veterinary Medicine in Hubei Province, Wuhan, Hubei, 430070, China.
  3. 3National Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, 430070, China. [email protected].
  4. 4Key Laboratory of Preventive Veterinary Medicine in Hubei Province, Wuhan, Hubei, 430070, China. [email protected].
  5. 5Hubei Jiangxia Laboratory, Wuhan, Hubei, 430200, China. [email protected].
  6. 6Hubei International Scientific and Technological Cooperation Base of Veterinary Epidemiology, Wuhan, Hubei, 430070, China. [email protected].
  7. 7National Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, 430070, China. [email protected].
  8. 8Key Laboratory of Preventive Veterinary Medicine in Hubei Province, Wuhan, Hubei, 430070, China. [email protected].
  9. 9Hubei International Scientific and Technological Cooperation Base of Veterinary Epidemiology, Wuhan, Hubei, 430070, China. [email protected].
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Abstract

Babesiosis is an increasingly recognized tick-borne zoonosis. The asexual blood stage of its causative agent, Babesia, drives pathological damages in the host and can cause severe or fatal human infections. Nevertheless, the transcriptional regulatory mechanisms that control this developmental stage remain poorly characterized. Here, we identified a novel ApiAP2 transcription factor (AP2-P; pathogenesis), which is essential in the blood-stage development of B. gibsoni. Nuclear import of AP2-P is inhibited by ivermectin, which is likely mediated via the IMPα/β pathway. Importantly, AP2-P forms a SAGA-like complex with the histone acetyltransferase GCN5 and a novel AP2-P related protein 1 (ARP1). Conditional knockdown of ARP1 or GCN5 results in reduced parasite growth rates accompanied by alterations in expression profiles and chromatin accessibility of pathogenesis-related genes. ChIP-seq data indicate that the complex associates with both euchromatic regions marked by H3K9ac and heterochromatic regions marked by H3K9me3, and it also targets many pathogenic genes by recognizing specific DNA motif, including those involved in invasion, antigenic variation, drug resistance, and sexual-stage development. Notably, normal genomic distribution pattern of AP2-P likewise depends on ARP1 or GCN5. Collectively, our study suggests a SAGA-like epigenetic module responsible for pathogenesis of Babesia gibsoni during asexual blood stage.

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Cite

BibTeXRIS
BibTeX
@article{han2026sagalike,
  title = {{A SAGA-like AP2-P-ARP1-GCN5 transcriptional complex targets pathogenesis-associated genes during the blood-stage development of Babesia gibsoni.}},
  author = {Zhen Han and Yaxin Zheng and Wei Liu and Wanxin Luo and Chenglong Wu and Jianyu Wang and Fangwei Chen and Lan He and Junlong Zhao},
  journal = {Nature communications},
  year = {2026},
  month = sep,
  doi = {10.1038/s41467-026-78127-2},
  url = {https://europepmc.org/article/MED/42957733},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - A SAGA-like AP2-P-ARP1-GCN5 transcriptional complex targets pathogenesis-associated genes during the blood-stage development of Babesia gibsoni.
AU  - Zhen Han
AU  - Yaxin Zheng
AU  - Wei Liu
AU  - Wanxin Luo
AU  - Chenglong Wu
AU  - Jianyu Wang
AU  - Fangwei Chen
AU  - Lan He
AU  - Junlong Zhao
PY  - 2026
DA  - 2026/09/29
JO  - Nature communications
DO  - 10.1038/s41467-026-78127-2
UR  - https://europepmc.org/article/MED/42957733
AB  - Babesiosis is an increasingly recognized tick-borne zoonosis. The asexual blood stage of its causative agent, Babesia, drives pathological damages in the host and can cause severe or fatal human infections. Nevertheless, the transcriptional regulatory mechanisms that control this developmental stage remain poorly characterized. Here, we identified a novel ApiAP2 transcription factor (AP2-P; pathogenesis), which is essential in the blood-stage development of B. gibsoni. Nuclear import of AP2-P is inhibited by ivermectin, which is likely mediated via the IMPα/β pathway. Importantly, AP2-P forms a SAGA-like complex with the histone acetyltransferase GCN5 and a novel AP2-P related protein 1 (ARP1). Conditional knockdown of ARP1 or GCN5 results in reduced parasite growth rates accompanied by alterations in expression profiles and chromatin accessibility of pathogenesis-related genes. ChIP-seq data indicate that the complex associates with both euchromatic regions marked by H3K9ac and heterochromatic regions marked by H3K9me3, and it also targets many pathogenic genes by recognizing specific DNA motif, including those involved in invasion, antigenic variation, drug resistance, and sexual-stage development. Notably, normal genomic distribution pattern of AP2-P likewise depends on ARP1 or GCN5. Collectively, our study suggests a SAGA-like epigenetic module responsible for pathogenesis of Babesia gibsoni during asexual blood stage.
SN  - 2041-1723
ER  -