4.7 Article

A Novel Multiprotein Bridging Factor 1-Like Protein Induces Cyst Wall Protein Gene Expression and Cyst Differentiation in Giardia lamblia

期刊

出版社

MDPI
DOI: 10.3390/ijms22031370

关键词

cyst; MBF1; transcription; Giardia; differentiation; DNA binding protein; parasite; transcription regulation

资金

  1. National Science Council [MOST 99-2320-B-002017-MY3, 100-2325-B-002-039, 101-2325-B-002-036-, 103-2628-B-002-006-MY3-, 106-2320-B-002 -038 -MY2, 109-2320-B-002-063-]
  2. National Health Research Institutes grant in Taiwan [NHRI-EX999510NC]
  3. Department of Medical Research in National Taiwan University Hospital
  4. Aim for the Top University Program of National Taiwan University [33474]

向作者/读者索取更多资源

The study revealed that Giardia's MBF1 gene plays a crucial role in cyst differentiation by binding to key promoter regions of cwp1-3 and myb2 genes and interacting with transcription factors to up-regulate cwp gene expression during encystation. This positive regulation of MBF1 in Giardia suggests a functional conservation of the gene in driving cyst formation.
The capacity to synthesize a protective cyst wall is critical for infectivity of Giardia lamblia. It is of interest to know the mechanism of coordinated synthesis of three cyst wall proteins (CWPs) during encystation, a differentiation process. Multiprotein bridging factor 1 (MBF1) gene family is a group of transcription coactivators that bridge various transcription factors. They are involved in cell growth and differentiation in yeast and animals, or in stress response in fungi and plants. We asked whether Giardia has MBF1-like genes and whether their products influence gene expression. BLAST searches of the Giardia genome database identified one gene encoding a putative MBF1 protein with a helix-turn-helix domain. We found that it can specifically bind to the AT-rich initiator promoters of the encystation-induced cwp1-3 and myb2 genes. MBF1 localized to cell nuclei and cytoplasm with higher expression during encystation. In addition, overexpression of MBF1 induced cwp1-3 and myb2 gene expression and cyst generation. Mutation of the helixes in the helix-turn-helix domain reduced cwp1-3 and myb2 gene expression and cyst generation. Chromatin immunoprecipitation assays confirmed the binding of MBF1 to the promoters with its binding sites in vivo. We also found that MBF1 can interact with E2F1, Pax2, WRKY, and Myb2 transcription factors that coordinately up-regulate the cwp genes during encystation. Using a CRISPR/Cas9 system for targeted disruption of mbf1 gene, we found a downregulation of cwp1-3 and myb2 genes and decrease of cyst generation. Our results suggest that MBF1 is functionally conserved and positively regulates Giardia cyst differentiation.

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