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Gene regulatory networks controlling functional activities of spatially and temporally distinct endodermal cell populations in the early mouse embryo remain ill defined. The T-box transcription factor Eomes, acting downstream from Nodal/Smad signals, directly activates the LIM domain homeobox transcription factor Lhx1 in the visceral endoderm. Here we demonstrate Smad4/Eomes-dependent Lhx1 expression in the epiblast marks the entire definitive endoderm lineage, the anterior mesendoderm, and midline progenitors. Conditional inactivation of Lhx1 disrupts anterior definitive endoderm development and impedes node and midline morphogenesis in part due to severe disturbances in visceral endoderm displacement. Transcriptional profiling and ChIP-seq (chromatin immunoprecipitation [ChIP] followed by high-throughput sequencing) experiments identified Lhx1 target genes, including numerous anterior definitive endoderm markers and components of the Wnt signaling pathway. Interestingly, Lhx1-binding sites were enriched at enhancers, including the Nodal-proximal epiblast enhancer element and enhancer regions controlling Otx2 and Foxa2 expression. Moreover, in proteomic experiments, we characterized a complex comprised of Lhx1, Otx2, and Foxa2 as well as the chromatin-looping protein Ldb1. These partnerships cooperatively regulate development of the anterior mesendoderm, node, and midline cell populations responsible for establishment of the left-right body axis and head formation.
Pubmed ID: 26494787 RIS Download
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Set of software modules for performing common ChIP-seq data analysis tasks across the whole genome, including positional correlation analysis, peak detection, and genome partitioning into signal-rich and signal-poor regions. The tools are designed to be simple, fast and highly modular. Each program carries out a well defined data processing procedure that can potentially fit into a pipeline framework. ChIP-Seq is also freely available on a Web interface.
View all literature mentionsBioinformatics resource system including web server and web service for functional annotation and enrichment analyses of gene lists. Consists of comprehensive knowledgebase and set of functional analysis tools. Includes gene centered database integrating heterogeneous gene annotation resources to facilitate high throughput gene functional analysis.
View all literature mentionsA software package for the mapping of short reads from illumina sequencing machines onto a reference genome. It''s recommended for most workflows, including those for genomic resequencing, RNA-Seq and Chip-seq. Stampy excels in the mapping of reads containing that contain sequence variation relative to the reference, in particular for those containing insertions or deletions. It can map reads from a highly divergent species to a reference genome for instance. Stampy achieves high sensitivity and speed by using a fast hashing algorithm and a detailed statistical model. Stampy has the following features: * Maps single, paired-end and mate pair Illumina reads to a reference genome * Fast: about 20 Gbase per hour in hybrid mode (using BWA) * Low memory footprint: 2.7 Gb shared memory for a 3Gbase genome * High sensitivity for indels and divergent reads, up to 10-15% * Low mapping bias for reads with SNPs * Well calibrated mapping quality scores * Input: Fastq and Fasta; gzipped or plain * Output: SAM, Maq''s map file * Optionally calculates per-base alignment posteriors * Optionally processes part of the input * Handles reads of up to 4500 bases
View all literature mentionsData analysis service that predicts functions of cis-regulatory regions identified by localized measurements of DNA binding events across an entire genome. Whereas previous methods took into account only binding proximal to genes, GREAT is able to properly incorporate distal binding sites and control for false positives using a binomial test over the input genomic regions. GREAT incorporates annotations from 20 ontologies and is available as a web application. The utility of GREAT extends to data generated for transcription-associated factors, open chromatin, localized epigenomic markers and similar functional data sets, and comparative genomics sets. Platform: Online tool
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