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Series GSE62786 Query DataSets for GSE62786
Status Public on Aug 27, 2015
Title Meis1 coordinates a network of genes implicated in eye development and microphthalmia
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary Microphthalmos is a rare congenital anomaly characterized by reduced eye size and visual deficits of variable degrees. Sporadic and hereditary microphthalmos has been associated to heterozygous mutations in genes fundamental for eye development. Yet, many cases are idiopathic or await the identification of molecular causes. Here we show that haploinsufficiency of Meis1, a transcription factor with an evolutionary conserved expression in the embryonic trunk, brain and sensory organs, including the eye, causes microphthalmic traits and visual impairment, in adult mice. In the trunk, Meis1 acts as a cofactor for genes of the Hox complex, mostly binding to Hox-Pbx target sequence on the DNA. By combining the analysis of Meis1 loss-of-function and conditional Meis1 functional rescue with ChIPseq and RNAseq approaches, we show that during the development of the optic cup, an Hox-free region, Meis1 binds instead to Hox/Pbx-independent Meis binding site, and coordinates, in a dose-dependent manner, retinal proliferation and differentiation by regulating the expression of components of the Notch signalling pathway. Meis1 also controls the activity of genes responsible for human microphthalmia and eye patterning so that in Meis1-/- embryos, the eye size is reduced and boundaries among the different eye territories are shifted or blurred. We thus propose that Meis1 is at the core of a genetic network implicated in microphthalmia, itself representing an additional candidate for syndromic cases of these ocular malformations.
Overall design Transcriptomics and Meis1 Occupancy analysis on mouse isolated optic cups and ChIP data for histone methylation marks were obtained from about 100 eyes of E10.5 CD1 embryos.

Contributor(s) Marcos S, González-Lázaro M, Beccari L, Carramolino L, Martín-Bermejo MJ, Amarie O, Mateos-San Martín D, Torroja C, Tena J, Doohan R, Puk O, Hrabě de Angelis M, Graw J, Gómez-Skarmeta JL, Casares F, Torres M, Boloventa P
Citation(s) 26253404
Submission date Oct 28, 2014
Last update date May 15, 2019
Contact name Carlos Torroja
Phone (+34) 91 4531200
Organization name Centro Nacional de Investigaciones Cardiovasculares (CNIC)
Department Bioinformatics Unit
Street address Melchor Fernandez Almagro, 3
City Madrid
State/province Madrid
ZIP/Postal code 28029
Country Spain
Platforms (2)
GPL11002 Illumina Genome Analyzer IIx (Mus musculus)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (5)
GSM1533392 KO_RNA-seq
GSM1533393 WT_RNA-seq
GSM1533394 Meis1_ChIP-seq
BioProject PRJNA265110
SRA SRP049351

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE62786_RAW.tar 940.0 Kb (http)(custom) TAR (of BED)
GSE62786_normalized_counts.txt.gz 265.7 Kb (ftp)(http) TXT
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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