Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0020088
Title: Mouse transgenesis identifies conserved functional enhancers and cis-regulatory motif in the vertebrate LIM homeobox gene Lhx2 locus
Authors: Lee A.P.
Brenner S. 
Venkatesh B. 
Keywords: LIM protein
transcription factor
DNA binding protein
homeodomain protein
LHX2 protein, human
Lhx2 protein, mouse
membrane protein
transcription factor
animal experiment
animal tissue
article
central nervous system
controlled study
Crb2 gene
embryo
enhancer region
gene control
gene expression profiling
gene function
gene locus
gene mutation
genetic conservation
genetic variability
human
human tissue
Lhx2 gene
mouse
neural tube
nonhuman
nucleotide sequence
prediction
protein motif
reporter gene
spinal ganglion
tissue specificity
transgenic mouse
transgenics
animal
animal embryo
chicken
genetics
in situ hybridization
metabolism
nucleotide sequence
vertebrate
Mammalia
Mus musculus
Pisces
Takifugu
Vertebrata
Animals
Chickens
Conserved Sequence
DNA-Binding Proteins
Embryo, Mammalian
Enhancer Elements, Genetic
Homeodomain Proteins
Humans
In Situ Hybridization
Membrane Proteins
Mice
Mice, Transgenic
Transcription Factors
Vertebrates
Issue Date: 2011
Citation: Lee A.P., Brenner S., Venkatesh B. (2011). Mouse transgenesis identifies conserved functional enhancers and cis-regulatory motif in the vertebrate LIM homeobox gene Lhx2 locus. PLoS ONE 6 (5) : e20088. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0020088
Rights: Attribution 4.0 International
Abstract: The vertebrate Lhx2 is a member of the LIM homeobox family of transcription factors. It is essential for the normal development of the forebrain, eye, olfactory system and liver as well for the differentiation of lymphoid cells. However, despite the highly restricted spatio-temporal expression pattern of Lhx2, nothing is known about its transcriptional regulation. In mammals and chicken, Crb2, Dennd1a and Lhx2 constitute a conserved linkage block, while the intervening Dennd1a is lost in the fugu Lhx2 locus. To identify functional enhancers of Lhx2, we predicted conserved noncoding elements (CNEs) in the human, mouse and fugu Crb2-Lhx2 loci and assayed their function in transgenic mouse at E11.5. Four of the eight CNE constructs tested functioned as tissue-specific enhancers in specific regions of the central nervous system and the dorsal root ganglia (DRG), recapitulating partial and overlapping expression patterns of Lhx2 and Crb2 genes. There was considerable overlap in the expression domains of the CNEs, which suggests that the CNEs are either redundant enhancers or regulating different genes in the locus. Using a large set of CNEs (810 CNEs) associated with transcription factor-encoding genes that express predominantly in the central nervous system, we predicted four over-represented 8-mer motifs that are likely to be associated with expression in the central nervous system. Mutation of one of them in a CNE that drove reporter expression in the neural tube and DRG abolished expression in both domains indicating that this motif is essential for expression in these domains. The failure of the four functional enhancers to recapitulate the complete expression pattern of Lhx2 at E11.5 indicates that there must be other Lhx2 enhancers that are either located outside the region investigated or divergent in mammals and fishes. Other approaches such as sequence comparison between multiple mammals are required to identify and characterize such enhancers. © 2011 Lee et al.
Source Title: PLoS ONE
URI: https://scholarbank.nus.edu.sg/handle/10635/162049
ISSN: 19326203
DOI: 10.1371/journal.pone.0020088
Rights: Attribution 4.0 International
Appears in Collections:Elements
Staff Publications

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
10_1371_journal_pone_0020088.pdf860.76 kBAdobe PDF

OPEN

NoneView/Download

Google ScholarTM

Check

Altmetric


This item is licensed under a Creative Commons License Creative Commons