RRC ID 79150
Author Ando K, Ou J, Thompson JD, Welsby J, Bangru S, Shen J, Wei X, Diao Y, Poss KD.
Title A screen for regeneration-associated silencer regulatory elements in zebrafish.
Journal 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.
Volume 59(5)
Pages 676-691.e5
Published 2024-3-11
DOI 10.1016/j.devcel.2024.01.004
PII S1534-5807(24)00004-2
PMID 38290519
PMC PMC10939760
MeSH Animals Animals, Genetically Modified Promoter Regions, Genetic Silencer Elements, Transcriptional* Zebrafish* / genetics
DNA material pcDNA3 Venus-Akaluc (RDB15781)