AUTHOR=Zhu Baicheng , Zhang Lu , Zhou Xinxin , Ning Hao , Ma Teng 

TITLE=Transcription factor ZNF22 regulates blood-tumor barrier permeability by interacting with HDAC3 protein

JOURNAL=Frontiers in Molecular Neuroscience

VOLUME=Volume 15 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/molecular-neuroscience/articles/10.3389/fnmol.2022.1027942

DOI=10.3389/fnmol.2022.1027942

ISSN=1662-5099

ABSTRACT=ZNF22 is a zinc finger transcription factor and HDAC3 is a histone deacetylase. In the present investigation, glioma-exposed endothelial cells (GECs) expressed higher levels of ZNF22 and HDAC3 than endothelial cells. We then affirmed that silencing HDAC3 or ZNF22 led to a reduction in blood tumor barrier (BTB) permeability. By bioinformatics analysis, chromatin immunoprecipitation (ChIP) assays and luciferase assay, we found that ZNF22 had a target binding relationship with the promoter regions of ZO-1, Occludin and Claudin-5 and negatively regulated the expression of ZO-1, Occludin and Claudin-5. Furthermore, we revealed that HDAC3, as a co-transcript repressor with histone deacetylase activity, could interact with ZNF22 to hinder the expression of TJ-associated proteins, thereby further facilitating the permeability of BTB. In summary, ZNF22 acted as a transcription factor in conjunction with HDAC3 to modulate the expression of TJ-associated proteins, which was correlated with an increase in BTB permeability. These results may provide new strategies and targets for the chemotherapy of gliomas as well as intracranial infections.