PUBLICATION

A screen for regeneration-associated silencer regulatory elements in zebrafish

Authors
Ando, K., Ou, J., Thompson, J.D., Welsby, J., Bangru, S., Shen, J., Wei, X., Diao, Y., Poss, K.D.
ID
ZDB-PUB-240131-2
Date
2024
Source
Developmental Cell   59(5): 676-691.e5 (Journal)
Registered Authors
Ando, Kazunori, Bangru, Sushant, Ou, Jianhong, Poss, Kenneth D., Shen, Jingwen, Thompson, John D.
Keywords
enhancer, fin regeneration, heart regeneration, regeneration, screen, silencer, zebrafish
Datasets
GEO:GSE231771, GEO:GSE231956
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Promoter Regions, Genetic
  • Silencer Elements, Transcriptional*
  • Zebrafish*/genetics
PubMed
38290519 Full text @ Dev. Cell
Abstract
Regeneration involves gene expression changes explained in part by context-dependent recruitment of transcriptional activators to distal enhancers. Silencers that engage repressive transcriptional complexes are less studied than enhancers and more technically challenging to validate, but they potentially have profound biological importance for regeneration. Here, we identified candidate silencers through a screening process that examined the ability of DNA sequences to limit injury-induced gene expression in larval zebrafish after fin amputation. A short sequence (s1) on chromosome 5 near several genes that reduce expression during adult fin regeneration could suppress promoter activity in stable transgenic lines and diminish nearby gene expression in knockin lines. High-resolution analysis of chromatin organization identified physical associations of s1 with gene promoters occurring preferentially during fin regeneration, and genomic deletion of s1 elevated the expression of these genes after fin amputation. Our study provides methods to identify "tissue regeneration silencer elements" (TRSEs) with the potential to reduce unnecessary or deleterious gene expression during regeneration.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping