ArticleNature communications2022
Etv2 regulates enhancer chromatin status to initiate Shh expression in the limb bud.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 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
15 citing papers in PubMed, 22 citations in OpenAlex.
- Article
- Distinct contributions of Etv2Cell reports · 2026Article
- The pioneer factor, ETV2, regulates networks to specify the embryonic endothelial lineage.Cardiovascular research · 2025Article
- A distal enhancer with ETV4 binding is critical for UCP1 expression and thermogenesis in brown fat.Genes & development · 2025Article
- The 3' region of the ZPA regulatory sequence (ZRS) is required for activity and contains a critical E-box.Frontiers in cell and developmental biology · 2025Article
- Evidence for Fgf and Wnt regulation ofFrontiers in cell and developmental biology · 2025Article
- ETV2 transcriptionally activates Rig1 gene expression and promotes reprogramming of the endothelial lineage.Scientific reports · 2024Article
- Development of a ZRS Reporter System for the Newt (Biomedicines · 2024Article
- Genetic variation is a key determinant of chromatin accessibility and drives differences in the regulatory landscape of C57BL/6J and 129S1/SvImJ mice.Nucleic acids research · 2024Article
- Functional categorization of gene regulatory variants that cause Mendelian conditions.Human genetics · 2024Review
- Sall4 regulates posterior trunk mesoderm development by promoting mesodermal gene expression and repressing neural genes in the mesoderm.Development (Cambridge, England) · 2024Article
- Recruitment of transcription factor ETS1 to activated accessible regions promotes the transcriptional program of cilia genes.Nucleic acids research · 2023Article
- Mendelian inheritance revisited: dominance and recessiveness in medical genetics.Nature reviews. Genetics · 2023Review
- SeATAC: a tool for exploring the chromatin landscape and the role of pioneer factors.Genome biology · 2023Article
- Evolutionary genetics of flipper forelimb and hindlimb loss from limb development-related genes in cetaceans.BMC genomics · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
Sonic hedgehog (Shh) is essential for limb development, and the mechanisms that govern the propagation and maintenance of its expression has been well studied; however, the mechanisms that govern the initiation of Shh expression are incomplete. Here we report that ETV2 initiates Shh expression by changing the chromatin status of the developmental limb enhancer, ZRS. Etv2 expression precedes Shh in limb buds, and Etv2 inactivation prevents the opening of limb chromatin, including the ZRS, resulting in an absence of Shh expression. Etv2 overexpression in limb buds causes nucleosomal displacement at the ZRS, ectopic Shh expression, and polydactyly. Areas of nucleosome displacement coincide with ETS binding site clusters. ETV2 also functions as a transcriptional activator of ZRS and is antagonized by ETV4/5 repressors. Known human polydactyl mutations introduce novel ETV2 binding sites in the ZRS, suggesting that ETV2 dosage regulates ZRS activation. These studies identify ETV2 as a pioneer transcription factor (TF) regulating the onset of Shh expression, having both a chromatin regulatory role and a transcriptional activation role.
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.