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Developmental gene clusters are paradigms for the study of gene regulation; however, the mechanisms that mediate phenomena such as coregulation and enhancer sharing remain largely elusive. Here we address this issue by analysing the vertebrate Irx clusters. We first present a deep enhancer screen of a 2-Mbp span covering the IrxA cluster. Using chromosome conformation capture, we show that enhancer sharing is widespread within the cluster, explaining its evolutionarily conserved organization. We also identify a three-dimensional architecture, probably formed through interactions with CCCTC-binding factor, which is present within both Irx clusters of mouse, Xenopus and zebrafish. This architecture brings the promoters of the first two genes together in the same chromatin landscape. We propose that this unique and evolutionarily conserved genomic architecture of the vertebrate Irx clusters is essential for the coregulation of the first two genes and simultaneously maintains the third gene in a partially independent regulatory landscape.
Figure 1 | Multiple enhancers are distributed along the the IrxA cluster. The black vertical line at the left depicts the IrxA cluster, showing coordinates
(kbp) of human chromosome 5. Columns show enhancer activity of different HCNRs in embryos of mouse (stage E11.5), Xenopus (stage 30) and zebrafish
(24 – 36 h.p.f.). Enhancers are named according to the coordinates (in kilobases) of their human HCNR counteparts. Orthologous regions promote
expression in largely equivalent territories. Arrowheads mark tissues by colour as follows: blue, midbrain; red, hindbrain; white, spinal cord; yellow, kidney;
and purple, otic vesicle.
Figure 5 | Disassembly of the IrxA cluster alters the expression patterns
of IrxA genes. Genome architecture and expression patterns of IrxA genes
in ( a ) Xenopus , ( b ) medaka and ( c ) zebrafish. Expression patterns at
neurula stages are shown in lateral and dorsal (insets) views. In a , b ,
numbers in parentheses indicate the intergenic distances, and in c it
represents the size of orthologous IrxAa DNA associated with each gene.
Red arrowheads point at Irx4 expression in the heart. Coloured rectangles:
enhancers analysed in this study by 3C. Some of these enhancers, as well
as others, were lost upon disaggregation of zebrafish IrxAa cluster. Scale
bars, 0.5 mm.
Alarcón,
A dual requirement for Iroquois genes during Xenopus kidney development.
2008, Pubmed,
Xenbase
Alarcón,
A dual requirement for Iroquois genes during Xenopus kidney development.
2008,
Pubmed
,
Xenbase
Bao,
CTCFBSDB: a CTCF-binding site database for characterization of vertebrate genomic insulators.
2008,
Pubmed
Becker,
Irx1 and Irx2 expression in early lung development.
2001,
Pubmed
,
Xenbase
Bellefroid,
Xiro3 encodes a Xenopus homolog of the Drosophila Iroquois genes and functions in neural specification.
1998,
Pubmed
,
Xenbase
Bessa,
Zebrafish enhancer detection (ZED) vector: a new tool to facilitate transgenesis and the functional analysis of cis-regulatory regions in zebrafish.
2009,
Pubmed
Birney,
Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project.
2007,
Pubmed
Bosse,
Identification of the vertebrate Iroquois homeobox gene family with overlapping expression during early development of the nervous system.
1997,
Pubmed
Dekker,
Capturing chromosome conformation.
2002,
Pubmed
de la Calle-Mustienes,
A functional survey of the enhancer activity of conserved non-coding sequences from vertebrate Iroquois cluster gene deserts.
2005,
Pubmed
,
Xenbase
Delgado-Olguín,
CTCF promotes muscle differentiation by modulating the activity of myogenic regulatory factors.
2011,
Pubmed
Dildrop,
Organization of Iroquois genes in fish.
2004,
Pubmed
Feijóo,
The Irx gene family in zebrafish: genomic structure, evolution and initial characterization of irx5b.
2004,
Pubmed
Ferraiuolo,
The three-dimensional architecture of Hox cluster silencing.
2010,
Pubmed
Garcia-Fernàndez,
The genesis and evolution of homeobox gene clusters.
2005,
Pubmed
Garriock,
Developmental expression of the Xenopus Iroquois-family homeobox genes, Irx4 and Irx5.
2001,
Pubmed
,
Xenbase
Gomez-Skarmeta,
Araucan and caupolican, two members of the novel iroquois complex, encode homeoproteins that control proneural and vein-forming genes.
1996,
Pubmed
Gómez-Skarmeta,
Xiro, a Xenopus homolog of the Drosophila Iroquois complex genes, controls development at the neural plate.
1998,
Pubmed
,
Xenbase
Gómez-Skarmeta,
Iroquois genes: genomic organization and function in vertebrate neural development.
2002,
Pubmed
Hagège,
Quantitative analysis of chromosome conformation capture assays (3C-qPCR).
2007,
Pubmed
Houweling,
Gene and cluster-specific expression of the Iroquois family members during mouse development.
2001,
Pubmed
Irimia,
Convergent evolution of clustering of Iroquois homeobox genes across metazoans.
2008,
Pubmed
Jeong,
A functional screen for sonic hedgehog regulatory elements across a 1 Mb interval identifies long-range ventral forebrain enhancers.
2006,
Pubmed
Kagey,
Mediator and cohesin connect gene expression and chromatin architecture.
2010,
Pubmed
Kawakami,
A transposon-mediated gene trap approach identifies developmentally regulated genes in zebrafish.
2004,
Pubmed
Kent,
The human genome browser at UCSC.
2002,
Pubmed
Kerner,
Evolutionary history of the iroquois/Irx genes in metazoans.
2009,
Pubmed
Lecaudey,
Expression of the zebrafish Iroquois genes during early nervous system formation and patterning.
2005,
Pubmed
Lettice,
A long-range Shh enhancer regulates expression in the developing limb and fin and is associated with preaxial polydactyly.
2003,
Pubmed
McEwen,
Ancient duplicated conserved noncoding elements in vertebrates: a genomic and functional analysis.
2006,
Pubmed
Murrell,
Interaction between differentially methylated regions partitions the imprinted genes Igf2 and H19 into parent-specific chromatin loops.
2004,
Pubmed
Nobrega,
Scanning human gene deserts for long-range enhancers.
2003,
Pubmed
,
Xenbase
Ogino,
High-throughput transgenesis in Xenopus using I-SceI meganuclease.
2006,
Pubmed
,
Xenbase
Peters,
Organization of mouse Iroquois homeobox genes in two clusters suggests a conserved regulation and function in vertebrate development.
2000,
Pubmed
,
Xenbase
Pittman,
The colorectal cancer risk at 18q21 is caused by a novel variant altering SMAD7 expression.
2009,
Pubmed
,
Xenbase
Portales-Casamar,
JASPAR 2010: the greatly expanded open-access database of transcription factor binding profiles.
2010,
Pubmed
Reggiani,
The prepattern transcription factor Irx3 directs nephron segment identity.
2007,
Pubmed
,
Xenbase
Rodríguez-Seguel,
The Xenopus Irx genes are essential for neural patterning and define the border between prethalamus and thalamus through mutual antagonism with the anterior repressors Fezf and Arx.
2009,
Pubmed
,
Xenbase
Rozen,
Primer3 on the WWW for general users and for biologist programmers.
2000,
Pubmed
Sharpe,
Selectivity, sharing and competitive interactions in the regulation of Hoxb genes.
1998,
Pubmed
Simonis,
An evaluation of 3C-based methods to capture DNA interactions.
2007,
Pubmed
Spitz,
Global control regions and regulatory landscapes in vertebrate development and evolution.
2008,
Pubmed
Spitz,
Inversion-induced disruption of the Hoxd cluster leads to the partition of regulatory landscapes.
2005,
Pubmed
Spitz,
A global control region defines a chromosomal regulatory landscape containing the HoxD cluster.
2003,
Pubmed
Splinter,
CTCF mediates long-range chromatin looping and local histone modification in the beta-globin locus.
2006,
Pubmed
Tolhuis,
Looping and interaction between hypersensitive sites in the active beta-globin locus.
2002,
Pubmed
Valadez-Graham,
CTCF-dependent enhancer blockers at the upstream region of the chicken alpha-globin gene domain.
2004,
Pubmed
Woolfe,
Highly conserved non-coding sequences are associated with vertebrate development.
2005,
Pubmed
Yee,
The regulation of myogenin gene expression during the embryonic development of the mouse.
1993,
Pubmed
Zülch,
Expression pattern of Irx1 and Irx2 during mouse digit development.
2001,
Pubmed
,
Xenbase
