Genome-wide binding of posterior HOXA/D transcription factors reveals subgrouping and association with CTCF

Jerković, Ivana; Ibrahim, Daniel Murad; Andrey, Guillaume; Haas, Stefan A.; Hansen, Peter; Janetzki, Catrin; González Navarrete, Irene, 1983-; Robinson, Peter N.; Hecht, Jochen; Mundlos, Stefan

Genome-wide binding of posterior HOXA/D transcription factors reveals subgrouping and association with CTCF

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dc.contributor.author Jerković, Ivanaca
dc.contributor.author Ibrahim, Daniel Muradca
dc.contributor.author Andrey, Guillaumeca
dc.contributor.author Haas, Stefan A.ca
dc.contributor.author Hansen, Peterca
dc.contributor.author Janetzki, Catrinca
dc.contributor.author González Navarrete, Irene, 1983-ca
dc.contributor.author Robinson, Peter N.ca
dc.contributor.author Hecht, Jochenca
dc.contributor.author Mundlos, Stefanca
dc.date.accessioned 2018-07-04T07:56:34Z
dc.date.available 2018-07-04T07:56:34Z
dc.date.issued 2017
dc.description.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.
dc.format.mimetype application/pdf
dc.identifier.citation Jerković I, Ibrahim DM, Andrey G, Haas S, Hansen P, Janetzki C et al. Genome-Wide Binding of Posterior HOXA/D Transcription Factors Reveals Subgrouping and Association with CTCF. PLoS Genet. 2017 Jan 19;13(1):e1006567. DOI: 10.1371/journal.pgen.1006567
dc.identifier.doi http://dx.doi.org/10.1371/journal.pgen.1006567
dc.identifier.issn 1553-7390
dc.identifier.uri http://hdl.handle.net/10230/35027
dc.language.iso eng
dc.publisher Public Library of Science (PLoS)ca
dc.relation.ispartof PLOS Genetics. 2017 Jan 19;13(1):e1006567
dc.rights This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication (http://creativecommons.org/publicdomain/zero/1.0/).
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.rights.uri http://creativecommons.org/publicdomain/zero/1.0/
dc.subject.keyword Gene expression regulation
dc.subject.keyword Homeobox
dc.subject.keyword Binding analysis
dc.subject.keyword Cell differentiation
dc.subject.keyword Sequence motif analysis
dc.subject.keyword Protein binding
dc.subject.keyword Chondrogenesis
dc.subject.keyword Chromatin
dc.subject.keyword Mesoderm
dc.title Genome-wide binding of posterior HOXA/D transcription factors reveals subgrouping and association with CTCFca
dc.type info:eu-repo/semantics/article
dc.type.version info:eu-repo/semantics/publishedVersion

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