PUBLICATION
Comparative genomic analysis of human GLI2 locus using slowly evolving fish revealed the ancestral gnathostome set of early developmental enhancers
- Authors
- Ali, S., Arif, I., Iqbal, A., Hussain, I., Abrar, M., Khan, M.R., Shubin, N., Abbasi, A.A.
- ID
- ZDB-PUB-210101-22
- Date
- 2020
- Source
- Developmental Dynamics : an official publication of the American Association of Anatomists 250(5): 669-683 (Journal)
- Registered Authors
- Shubin, Neil
- Keywords
- CNEs, Elelphant shark, Enhancers, Gar, Gli family, Gli2, Gnathostomes, Hh signaling, Transgenesis, Zebrafish
- MeSH Terms
-
- Animals
- Biological Evolution*
- Fishes/genetics*
- Fishes/growth & development*
- Humans
- Zinc Finger Protein Gli2/genetics*
- PubMed
- 33381902 Full text @ Dev. Dyn.
Citation
Ali, S., Arif, I., Iqbal, A., Hussain, I., Abrar, M., Khan, M.R., Shubin, N., Abbasi, A.A. (2020) Comparative genomic analysis of human GLI2 locus using slowly evolving fish revealed the ancestral gnathostome set of early developmental enhancers. Developmental Dynamics : an official publication of the American Association of Anatomists. 250(5):669-683.
Abstract
Background The zinc finger-containing transcription factor Gli2, is a key mediator of Hedgehog (Hh) signaling and participates in embryonic patterning of various organs including the central nervous system (CNS) and limbs. Abnormal expression of Gli2 can impede the transcription of Hh target genes through disruption of proper balance between Gli2 and Gli3 functions. Therefore, delineation of enhancers that are required for complementary roles of Glis would allow the interrogation of those pathogeneic variants that cause gene dysregulation, and a corresponding abnormal phenotype. Previously, we reported tissue-specific enhancers for Gli family including Gli2 through direct tetrapod-teleost comparisons.
Results Here, we employed the sequence alignments of slowly evolving spotted gar and elephant shark and have identified six novel conserved non-coding elements in human GLI2 containing locus. Zebrafish-based transgenic assays revealed that combined action of these autonomous CNEs reflects many aspects of Gli2 specific endogenous transcriptional activity, including CNS and pectoral fins.
Conclusion Taken together with our previous findings, this study suggests that Hh-signaling controlled deployment of Gli2 activity in embryonic patterning arose in the common ancestor of gnathostomes. These GLI2 specific cis-regulatory modules will help to identify DNA variants that probably reside outside of coding intervals and are associated with congenital anomalies. This article is protected by copyright. All rights reserved.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping