PUBLICATION
Negative Elongation Factor (NELF) Inhibits Premature Granulocytic Development in Zebrafish
- Authors
- Huang, M., Ahmed, A., Wang, W., Wang, X., Ma, C., Jiang, H., Li, W., Jing, L.
- ID
- ZDB-PUB-220413-14
- Date
- 2022
- Source
- International Journal of Molecular Sciences 23(7): (Journal)
- Registered Authors
- Jing, Lili
- Keywords
- RNA polymerase II promoter proximal pausing, granulocytic development, negative elongation factor, zebrafish
- MeSH Terms
-
- Animals
- Gene Expression Regulation
- RNA Polymerase II/genetics
- Transcription Factors*/metabolism
- Transcription, Genetic
- Zebrafish*/genetics
- Zebrafish*/metabolism
- Zebrafish Proteins
- PubMed
- 35409193 Full text @ Int. J. Mol. Sci.
Citation
Huang, M., Ahmed, A., Wang, W., Wang, X., Ma, C., Jiang, H., Li, W., Jing, L. (2022) Negative Elongation Factor (NELF) Inhibits Premature Granulocytic Development in Zebrafish. International Journal of Molecular Sciences. 23(7):.
Abstract
Gene expression is tightly regulated during hematopoiesis. Recent studies have suggested that RNA polymerase II (Pol II) promoter proximal pausing, a temporary stalling downstream of the promoter region after initiation, plays a critical role in regulating the expression of various genes in metazoans. However, the function of proximal pausing in hematopoietic gene regulation remains largely unknown. The negative elongation factor (NELF) complex is a key factor important for this proximal pausing. Previous studies have suggested that NELF regulates granulocytic differentiation in vitro, but its in vivo function during hematopoiesis remains uncharacterized. Here, we generated the zebrafish mutant for one NELF complex subunit Nelfb using the CRISPR-Cas9 technology. We found that the loss of nelfb selectively induced excessive granulocytic development during primitive and definitive hematopoiesis. The loss of nelfb reduced hematopoietic progenitor cell formation and did not affect erythroid development. Moreover, the accelerated granulocytic differentiation and reduced progenitor cell development could be reversed by inhibiting Pol II elongation. Further experiments demonstrated that the other NELF complex subunits (Nelfa and Nelfe) played similar roles in controlling granulocytic development. Together, our studies suggested that NELF is critical in controlling the proper granulocytic development in vivo, and that promoter proximal pausing might help maintain the undifferentiated state of hematopoietic progenitor cells.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping