ArticleGenome research2013
Distinct global shifts in genomic binding profiles of limb malformation-associated HOXD13 mutations.
Article in Genome research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 37 citations in OpenAlex.
- Missense variants in human forkhead transcription factors reveal determinants of forkhead DNA bispecificity.Cell reports · 2025Article
- HOXA5-driven transcriptional program in lung development.Developmental biology · 2025Article
- NKX2-5 congenital heart disease mutations show diverse loss and gain of epigenomic, biochemical and chromatin search functions underpinning pathogenicity.bioRxiv : the preprint server for biology · 2025Article
- Missense variants in human forkhead transcription factors reveal determinants of forkhead DNA bispecificity.bioRxiv : the preprint server for biology · 2025Article
- HOXA9 versus HOXB9; particular focus on their controversial role in tumor pathogenesis.Journal of applied genetics · 2024Review
- DNA binding analysis of rare variants in homeodomains reveals homeodomain specificity-determining residues.Nature communications · 2024Article
- A novel Hoxd13 mutation causes synpolydactyly and promotes osteoclast differentiation by regulating pSmad5/p65/c-Fos/Rank axis.Cell death & disease · 2023Article
- Article
- Article
- Article
- Specificity landscapes unmask submaximal binding site preferences of transcription factors.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Ancient mechanisms for the evolution of the bicoid homeodomain's function in fly development.eLife · 2018Article
- Efficient generation of mouse models of human diseases via ABE- and BE-mediated base editing.Nature communications · 2018Article
- A dual transcript-discovery approach to improve the delimitation of gene features from RNA-seq data in the chicken model.Biology open · 2018Article
- Genome-Wide Binding of Posterior HOXA/D Transcription Factors Reveals Subgrouping and Association with CTCF.PLoS genetics · 2017Article
- An interdigit signalling centre instructs coordinate phalanx-joint formation governed by 5'Hoxd-Gli3 antagonism.Nature communications · 2016Article
- First insights into the nature and evolution of antisense transcription in nematodes.BMC evolutionary biology · 2016Article
- Survey of variation in human transcription factors reveals prevalent DNA binding changes.Science (New York, N.Y.) · 2016Article
- Saturation analysis of ChIP-seq data for reproducible identification of binding peaks.Genome research · 2015Article
- Brachydactyly Type C patient with compound heterozygosity for p.Gly319Val and p.Ile358Thr variants in the GDF5 proregion: benign variants or mutations?Journal of human genetics · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gene regulation by transcription factors (TFs) determines developmental programs and cell identity. Consequently, mutations in TFs can lead to dramatic phenotypes in humans by disrupting gene regulation. To date, the molecular mechanisms that actually cause these phenotypes have been difficult to address experimentally. ChIP-seq, which couples chromatin immunoprecipitation with high-throughput sequencing, allows TF function to be investigated on a genome-wide scale, enabling new approaches for the investigation of gene regulation. Here, we present the application of ChIP-seq to explore the effect of missense mutations in TFs on their genome-wide binding profile. Using a retroviral expression system in chicken mesenchymal stem cells, we elucidated the mechanism underlying a novel missense mutation in HOXD13 (Q317K) associated with a complex hand and foot malformation phenotype. The mutated glutamine (Q) is conserved in most homeodomains, a notable exception being bicoid-type homeodomains that have lysine (K) at this position. Our results show that the mutation results in a shift in the binding profile of the mutant toward a bicoid/PITX1 motif. Gene expression analysis and functional assays using in vivo overexpression studies confirm that the mutation results in a partial conversion of HOXD13 into a TF with bicoid/PITX1 properties. A similar shift was not observed with another mutation, Q317R, which is associated with brachysyndactyly, suggesting that the bicoid/PITX1-shift observed for Q317K might be related to the severe clinical phenotype. The methodology described can be used to investigate a wide spectrum of TFs and mutations that have not previously been amenable to ChIP-seq experiments.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.