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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.
Pubmed ID: 21629789 RIS Download
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Collection of genome databases for vertebrates and other eukaryotic species with DNA and protein sequence search capabilities. Used to automatically annotate genome, integrate this annotation with other available biological data and make data publicly available via web. Ensembl tools include BLAST, BLAT, BioMart and the Variant Effect Predictor (VEP) for all supported species.
View all literature mentionsWelcome to Michael Eisens lab in the Howard Hughes Medical Institute (HHMI) at University of California at Berkeley (UCB) and the Lawrence Berkeley National Lab (LBNL). We are part of the Department of Molecular and Cell Biology of UCB and the Genomics Division of LBNL, and the. We are located in Stanley Hall on the Berkeley campus.Our lab applies computational and experimental genomic approaches to study how genome sequences specify organismal form and function. We are particularly interested in the regulation of gene expression, and focus on how the information that specifies when and where genes are expressed is encoded in genome sequences, the role that regulated gene expression plays in animal development and the response of microbes to their environments, and how variation in and evolution of gene expression contributes to phenotypic variation and the remarkable diversity of life on Earth. This site contains a more detailed description of our research projects, an introduction to members of the lab, reprints of all of our publications, free downloadable and web-based software. Sponsor. Experimental work described here was supported by a Howard Hughes Medical Institute Investigator award to MBE and by National Institutes of Health (NIH) grant GM704403 to MBE and MDB. Computational analyses were supported in by NIH grant HG002779 to MBE. Work at Lawrence Berkeley National Laboratory was conducted under Department of Energy contract DE-AC02-05CH11231. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
View all literature mentionsCentral online repository for microRNA nomenclature, sequence data, annotation and target prediction.Collection of published miRNA sequences and annotation.
View all literature mentionsSoftware to graphically browse results of clustering and other analyses from Cluster.
View all literature mentionsSoftware R package. Methods for Cluster analysis. Performs variety of types of cluster analysis and other types of processing on large microarray datasets.
View all literature mentionsDatabase of associations between traits and variants using UK Biobank cohort. Searchable atlas of genetic associations. Assists researchers to query UK Biobank. Provides unbiased view of phenotype and genotype associations across of traits.
View all literature mentionsMus musculus with name FVB/NJ from IMSR.
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