PUBLICATION
Activator-blocker model of transcriptional regulation by pioneer-like factors
- Authors
- Riesle, A.J., Gao, M., Rosenblatt, M., Hermes, J., Hass, H., Gebhard, A., Veil, M., Grüning, B., Timmer, J., Onichtchouk, D.
- ID
- ZDB-PUB-230915-59
- Date
- 2023
- Source
- Nature communications 14: 56775677 (Journal)
- Registered Authors
- Onichtchouk, Daria, Veil, Marina
- Keywords
- none
- Datasets
- GEO:GSE188364, GEO:GSE162415, GEO:GSE143439, GEO:GSE215956
- MeSH Terms
-
- Animals
- Gene Expression Regulation
- Histones*/genetics
- Mammals
- Transcription Factors/genetics
- Transcriptional Activation
- Zebrafish*/genetics
- PubMed
- 37709752 Full text @ Nat. Commun.
Citation
Riesle, A.J., Gao, M., Rosenblatt, M., Hermes, J., Hass, H., Gebhard, A., Veil, M., Grüning, B., Timmer, J., Onichtchouk, D. (2023) Activator-blocker model of transcriptional regulation by pioneer-like factors. Nature communications. 14:56775677.
Abstract
Zygotic genome activation (ZGA) in the development of flies, fish, frogs and mammals depends on pioneer-like transcription factors (TFs). Those TFs create open chromatin regions, promote histone acetylation on enhancers, and activate transcription. Here, we use the panel of single, double and triple mutants for zebrafish genome activators Pou5f3, Sox19b and Nanog, multi-omics and mathematical modeling to investigate the combinatorial mechanisms of genome activation. We show that Pou5f3 and Nanog act differently on synergistic and antagonistic enhancer types. Pou5f3 and Nanog both bind as pioneer-like TFs on synergistic enhancers, promote histone acetylation and activate transcription. Antagonistic enhancers are activated by binding of one of these factors. The other TF binds as non-pioneer-like TF, competes with the activator and blocks all its effects, partially or completely. This activator-blocker mechanism mutually restricts widespread transcriptional activation by Pou5f3 and Nanog and prevents premature expression of late developmental regulators in the early embryo.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping