PUBLICATION
The landscape of pioneer factor activity reveals the mechanisms of chromatin reprogramming and genome activation
- Authors
- Miao, L., Tang, Y., Bonneau, A.R., Chan, S.H., Kojima, M.L., Pownall, M.E., Vejnar, C.E., Gao, F., Krishnaswamy, S., Hendry, C.E., Giraldez, A.J.
- ID
- ZDB-PUB-220220-2
- Date
- 2022
- Source
- Molecular Cell 82(5): 986-1002.e9 (Journal)
- Registered Authors
- Giraldez, Antonio, Vejnar, Charles
- Keywords
- chromatin accessibility, chromatin reprogramming, genome activation, histone acetylation, nucleosome occupancy, pioneer transcription factors
- MeSH Terms
-
- Animals
- Chromatin*/genetics
- Genome/genetics
- Histones/genetics
- Histones/metabolism
- Nucleosomes*/genetics
- SOX Transcription Factors/genetics
- SOX Transcription Factors/metabolism
- Zebrafish/genetics
- Zebrafish/metabolism
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 35182480 Full text @ Mol. Cell
Citation
Miao, L., Tang, Y., Bonneau, A.R., Chan, S.H., Kojima, M.L., Pownall, M.E., Vejnar, C.E., Gao, F., Krishnaswamy, S., Hendry, C.E., Giraldez, A.J. (2022) The landscape of pioneer factor activity reveals the mechanisms of chromatin reprogramming and genome activation. Molecular Cell. 82(5):986-1002.e9.
Abstract
Upon fertilization, embryos undergo chromatin reprogramming and genome activation; however, the mechanisms that regulate these processes are poorly understood. Here, we generated a triple mutant for Nanog, Pou5f3, and Sox19b (NPS) in zebrafish and found that NPS pioneer chromatin opening at >50% of active enhancers. NPS regulate acetylation across core histones at enhancers and promoters, and their function in gene activation can be bypassed by recruiting histone acetyltransferase to individual genes. NPS pioneer chromatin opening individually, redundantly, or additively depending on sequence context, and we show that high nucleosome occupancy facilitates NPS pioneering activity. Nucleosome position varies based on the input of different transcription factors (TFs), providing a flexible platform to modulate pioneering activity. Altogether, our results illuminate the sequence of events during genome activation and offer a conceptual framework to understand how pioneer factors interpret the genome and integrate different TF inputs across cell types and developmental transitions.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping