PUBLICATION

An evolutionarily conserved three-dimensional structure in the vertebrate Irx clusters facilitates enhancer sharing and coregulation

Authors
Tena, J.J., Alonso, M.E., de la Calle-Mustienes, E., Splinter, E., de Laat, W., Manzanares, M., and Gómez-Skarmeta, J.L.
ID
ZDB-PUB-110523-27
Date
2011
Source
Nature communications   2: 310 (Journal)
Registered Authors
de la Calle-Mustienes, Elisa, Gómez-Skarmeta, José Luis, Tena, Juan
Keywords
none
MeSH Terms
  • Animals
  • Conserved Sequence/genetics
  • Evolution, Molecular*
  • Gene Expression Regulation, Developmental*
  • Homeodomain Proteins/genetics*
  • Mice
  • Multigene Family*
  • Promoter Regions, Genetic*
  • Repressor Proteins/genetics
  • Transcription Factors/genetics
  • Xenopus/embryology
  • Xenopus/genetics*
  • Xenopus Proteins/genetics
  • Zebrafish/embryology
  • Zebrafish/genetics*
  • Zebrafish Proteins/genetics
(all 16)
PubMed
21556064 Full text @ Nat. Commun.
Abstract
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.
Genes / Markers
Marker Marker Type Name
ctcfGENECCCTC-binding factor (zinc finger protein)
gata2aGENEGATA binding protein 2a
irx1aGENEiroquois homeobox 1a
irx2aGENEiroquois homeobox 2a
irx3aGENEiroquois homeobox 3a
irx4aGENEiroquois homeobox 4a
irx5aGENEiroquois homeobox 5a
irx6aGENEiroquois homeobox 6a
1 - 8 of 8
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Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
No data available
Sequence Targeting Reagents
Target Reagent Reagent Type
ctcfMO3-ctcfMRPHLNO
ctcfMO5-ctcfMRPHLNO
1 - 2 of 2
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Fish
Antibodies
No data available
Orthology
Engineered Foreign Genes
Marker Marker Type Name
DsRedEFGDsRed
EGFPEFGEGFP
1 - 2 of 2
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Mapping