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  Genome-Wide Binding of Posterior HOXA/D Transcription Factors Reveals Subgrouping and Association with CTCF

Jerković, I., Ibrahim, D., Andrey, G., Haas, S., Hansen, P., Janetzki, C., et al. (2017). Genome-Wide Binding of Posterior HOXA/D Transcription Factors Reveals Subgrouping and Association with CTCF. PLoS Genetics, 13(1): e1006567. doi:10.1371/journal.pgen.1006567.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0000-8129-0 Version Permalink: http://hdl.handle.net/21.11116/0000-0000-812A-F
Genre: Journal Article

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 Creators:
Jerković, I.1, Author
Ibrahim, D.1, Author              
Andrey, G.1, Author
Haas, S.2, Author              
Hansen, P., Author
Janetzki, C., Author
Gonzalez Navarrete, I., Author
Robinson, P. N., Author
Hecht, J.1, Author              
Mundlos, S.1, Author              
Affiliations:
1Research Group Development & Disease (Head: Stefan Mundlos), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433557              
2Gene Structure and Array Design (Stefan Haas), Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479640              

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Free keywords: Animals CCCTC-Binding Factor Chickens Chondrogenesis Chromatin/metabolism *Gene Expression Regulation, Developmental *Genome Homeodomain Proteins/*metabolism Mesoderm/metabolism Protein Binding Repressor Proteins/*metabolism *Transcriptional Activation
 Abstract: Homeotic genes code for key transcription factors (HOX-TFs) that pattern the animal body plan. During embryonic development, Hox genes are expressed in overlapping patterns and function in a partially redundant manner. In vitro biochemical screens probing the HOX-TF sequence specificity revealed largely overlapping sequence preferences, indicating that co-factors might modulate the biological function of HOX-TFs. However, due to their overlapping expression pattern, high protein homology, and insufficiently specific antibodies, little is known about their genome-wide binding preferences. In order to overcome this problem, we virally expressed tagged versions of limb-expressed posterior HOX genes (HOXA9-13, and HOXD9-13) in primary chicken mesenchymal limb progenitor cells (micromass). We determined the effect of each HOX-TF on cellular differentiation (chondrogenesis) and gene expression and found that groups of HOX-TFs induce distinct regulatory programs. We used ChIP-seq to determine their individual genome-wide binding profiles and identified between 12,721 and 28,572 binding sites for each of the nine HOX-TFs. Principal Component Analysis (PCA) of binding profiles revealed that the HOX-TFs are clustered in two subgroups (Group 1: HOXA/D9, HOXA/D10, HOXD12, and HOXA13 and Group 2: HOXA/D11 and HOXD13), which are characterized by differences in their sequence specificity and by the presence of cofactor motifs. Specifically, we identified CTCF binding sites in Group 1, indicating that this subgroup of HOX-proteins cooperates with CTCF. We confirmed this interaction by an independent biological assay (Proximity Ligation Assay) and demonstrated that CTCF is a novel HOX cofactor that specifically associates with Group 1 HOX-TFs, pointing towards a possible interplay between HOX-TFs and chromatin architecture.

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Language(s): eng - English
 Dates: 2017-01-042017-01-19
 Publication Status: Published online
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 Table of Contents: -
 Rev. Method: -
 Identifiers: DOI: 10.1371/journal.pgen.1006567
ISSN: 1553-7404 (Electronic)
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Title: PLoS Genetics
  Other : PLoS Genet.
Source Genre: Journal
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Publ. Info: San Francisco, CA : Public Library of Science
Pages: - Volume / Issue: 13 (1) Sequence Number: e1006567 Start / End Page: - Identifier: ISSN: 1553-7390
CoNE: /journals/resource/1000000000017180