Evidence map›Paper›PMID 26814189›Full record

ArticleMolecular biology and evolution2016

Human Lineage-Specific Transcriptional Regulation through GA-Binding Protein Transcription Factor Alpha (GABPa).

Alvaro Perdomo-Sabogal, Katja Nowick, Ilaria Piccini, Ralf Sudbrak, Hans Lehrach, Marie-Laure Yaspo, Hans-Jörg Warnatz, Robert Querfurth

Open access · bronzeAbstract read
In one paragraph

Article in Molecular biology and evolution, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
2.1field-weighted citation impact, top 13% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed, 44 citations in OpenAlex.

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  4. GABPα inhibits tumor progression and angiogenesis via a novel 18-bp indel withinCancer biomarkers : section A of Disease markers · 2024
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  14. Catalytic deficiency of O-GlcNAc transferase leads to X-linked intellectual disability.Proceedings of the National Academy of Sciences of the United States of America · 2019
    Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 2 countries.

Alvaro Perdomo-SabogalBioinformatics Group, Department of Computer Science, and Interdisciplinary Center for Bioinformatics, University Leipzig, Leipzig, Germany Paul-Flechsig Institute for Brain Research, University of Leipzig, Leipzig, Germany.
Katja NowickBioinformatics Group, Department of Computer Science, and Interdisciplinary Center for Bioinformatics, University Leipzig, Leipzig, Germany Paul-Flechsig Institute for Brain Research, University of Leipzig, Leipzig, Germany nowick@bioinf.uni-leipzig.de Robert.Querfurth@gmx.de.
Ilaria PicciniInstitute of Genetics of Heart Diseases (IfGH), Department of Cardiovascular Medicine, University Hospital Münster, 48149 Münster, Germany Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany.
Ralf SudbrakEuropean Centre for Public Heath Genomics, UNU-MERIT, Unsiversity Maastricht,PO Box 616, 6200 MD Maastricht, The Netherlands Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany.
Hans LehrachDepartment of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany.
Marie-Laure YaspoDepartment of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany.
Hans-Jörg WarnatzDepartment of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany.
Robert QuerfurthDepartment of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany nowick@bioinf.uni-leipzig.de Robert.Querfurth@gmx.de.
Max Planck Institute for Molecular Genetics · DELeipzig University · DEUniversity Hospital Münster · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

A substantial fraction of phenotypic differences between closely related species are likely caused by differences in gene regulation. While this has already been postulated over 30 years ago, only few examples of evolutionary changes in gene regulation have been verified. Here, we identified and investigated binding sites of the transcription factor GA-binding protein alpha (GABPa) aiming to discover cis-regulatory adaptations on the human lineage. By performing chromatin immunoprecipitation-sequencing experiments in a human cell line, we found 11,619 putative GABPa binding sites. Through sequence comparisons of the human GABPa binding regions with orthologous sequences from 34 mammals, we identified substitutions that have resulted in 224 putative human-specific GABPa binding sites. To experimentally assess the transcriptional impact of those substitutions, we selected four promoters for promoter-reporter gene assays using human and African green monkey cells. We compared the activities of wild-type promoters to mutated forms, where we have introduced one or more substitutions to mimic the ancestral state devoid of the GABPa consensus binding sequence. Similarly, we introduced the human-specific substitutions into chimpanzee and macaque promoter backgrounds. Our results demonstrate that the identified substitutions are functional, both in human and nonhuman promoters. In addition, we performed GABPa knock-down experiments and found 1,215 genes as strong candidates for primary targets. Further analyses of our data sets link GABPa to cognitive disorders, diabetes, KRAB zinc finger (KRAB-ZNF), and human-specific genes. Thus, we propose that differences in GABPa binding sites played important roles in the evolution of human-specific phenotypes.

Indexed as

Gene Expression RegulationAnimalsBinding SitesBiological EvolutionChlorocebus aethiopsChromatin ImmunoprecipitationChromosome MappingCOS CellsEvolution, MolecularGA-Binding Protein Transcription FactorGenetic SpeciationHEK293 CellsHumansPromoter Regions, GeneticProtein BindingSequence AlignmentGA-Binding Protein Transcription FactorGABPA protein, humanChIP-Seqcomparative genomics.GABPhuman molecular evolutionhuman-specific binding sitesKRAB zinc finger genespromoter assay

Identifiers

PMID26814189
PMCPMC4839217
OpenAlexW2283648003

What OpenQuestion holds

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LicenceCC BY-NC
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Registered trials

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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.