PUBLICATION
Znf687 recruits Brd4-Smrt complex to regulate gfi1aa during neutrophil development
- Authors
- Yan, L., Tan, S., Wang, H., Yuan, H., Liu, X., Chen, Y., de Thé, H., Zhu, J., Zhou, J.
- ID
- ZDB-PUB-240208-14
- Date
- 2024
- Source
- Leukemia 38(4): 851-864 (Journal)
- Registered Authors
- Chen, Yi, Zhu, Jun
- Keywords
- none
- MeSH Terms
-
- Animals
- Bromodomain Containing Proteins
- Cell Cycle Proteins/genetics
- Cell Cycle Proteins/metabolism
- DNA-Binding Proteins/genetics
- DNA-Binding Proteins/metabolism
- Neutrophils*/metabolism
- Nuclear Proteins/genetics
- Nuclear Proteins/metabolism
- Transcription Factors*/genetics
- Transcription Factors*/metabolism
- Zebrafish/metabolism
- PubMed
- 38326409 Full text @ Leukemia
Citation
Yan, L., Tan, S., Wang, H., Yuan, H., Liu, X., Chen, Y., de Thé, H., Zhu, J., Zhou, J. (2024) Znf687 recruits Brd4-Smrt complex to regulate gfi1aa during neutrophil development. Leukemia. 38(4):851-864.
Abstract
Neutrophils are key component of the innate immune system in vertebrates. Diverse transcription factors and cofactors act in a well-coordinated manner to ensure proper neutrophil development. Dysregulation of the transcriptional program triggering neutrophil differentiation is associated with various human hematologic disorders such as neutropenia, neutrophilia, and leukemia. In the current study we show the zinc finger protein Znf687 is a lineage-preferential transcription factor, whose deficiency leads to an impaired neutrophil development in zebrafish. Mechanistically, Znf687 functions as a negative regulator of gfi1aa, a pivotal modulator in terminal granulopoiesis, to regulate neutrophil maturation. Moreover, we found BRD4, an important epigenetic regulator, directly interacts with ZNF687 in neutrophils. Deficiency of brd4 results in similar defective neutrophil development as observed in znf687 mutant zebrafish. Biochemical and genetic analyses further reveal that instead of serving as a canonical transcriptional coactivator, Brd4 directly interacts and bridges Znf687 and Smrt nuclear corepressor on gfi1aa gene's promoter to exert transcription repression. In addition, the ZNF687-BRD4-SMRT-GFI1 transcriptional regulatory network is evolutionary conserved in higher vertebrate. Overall, our work indicates Znf687 and Brd4 are two novel master regulators in promoting terminal granulopoiesis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping