PUBLICATION
Analysis of the wnt1 regulatory chromosomal landscape
- Authors
- Lekven, A.C., Lilie, C.J., Gibbs, H.C., Green, D.G., Singh, A., Yeh, A.T.
- ID
- ZDB-PUB-190303-8
- Date
- 2019
- Source
- Development genes and evolution 229(2-3): 43-52 (Journal)
- Registered Authors
- Lekven, Arne
- Keywords
- ATAC-seq, CAGE-seq, Cis-regulation, Conserved non-coding element, Neural patterning, Spotted gar, Vertebrate, Zebrafish, wnt1, wnt10b
- MeSH Terms
-
- Animals
- Brain/embryology*
- Chromatin
- Embryo, Nonmammalian/metabolism
- Fish Proteins/genetics
- Fish Proteins/metabolism
- Fishes/embryology
- Fishes/genetics
- Gene Expression Regulation, Developmental
- Genomics
- Mice
- Promoter Regions, Genetic
- Regulatory Elements, Transcriptional*
- Wnt Proteins/genetics*
- Wnt Proteins/metabolism
- Zebrafish/embryology*
- Zebrafish/metabolism
- Zebrafish Proteins/genetics*
- Zebrafish Proteins/metabolism
- PubMed
- 30825002 Full text @ Dev. Genes Evol.
Citation
Lekven, A.C., Lilie, C.J., Gibbs, H.C., Green, D.G., Singh, A., Yeh, A.T. (2019) Analysis of the wnt1 regulatory chromosomal landscape. Development genes and evolution. 229(2-3):43-52.
Abstract
One of the earliest patterning events in the vertebrate neural plate is the specification of mes/r1, the territory comprising the prospective mesencephalon and the first hindbrain rhombomere. Within mes/r1, an interface of gene expression defines the midbrain-hindbrain boundary (MHB), a lineage restriction that separates the mesencephalon and rhombencephalon. wnt1 is critical to mes/r1 development and functions within the MHB as a component of the MHB gene regulatory network (GRN). Despite its importance to these critical and early steps of vertebrate neurogenesis, little is known about the factors responsible for wnt1 transcriptional regulation. In the zebrafish, wnt1 and its neighboring paralog, wnt10b, are expressed in largely overlapping patterns, suggesting co-regulation. To understand wnt1 and wnt10b transcriptional control, we used a comparative genomics approach to identify relevant enhancers. We show that the wnt1-wnt10b locus contains multiple cis-regulatory elements that likely interact to generate the wnt1 and wnt10b expression patterns. Two of 11 conserved enhancers tested show activity restricted to the midbrain and MHB, an activity that is conserved in the distantly related spotted gar orthologous elements. Three non-conserved elements also play a likely role in wnt1 regulation. The identified enhancers display dynamic modes of chromatin accessibility, suggesting controlled deployment during embryogenesis. Our results suggest that the control of wnt1 and wnt10b expression is under complex regulation involving the interaction of multiple enhancers.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping