Evidence map›Paper›PMID 23054834›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2012

Basic leucine zipper transcription factor Hac1 binds DNA in two distinct modes as revealed by microfluidic analyses.

Polly M Fordyce, David Pincus, Philipp Kimmig, Christopher S Nelson, Hana El-Samad, Peter Walter, Joseph L DeRisi

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed
2.7field-weighted citation impact, top 10% 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

43 citing papers in PubMed, 78 citations in OpenAlex.

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  7. Tailored UPRE2 variants for dynamic gene regulation in yeast.Proceedings of the National Academy of Sciences of the United States of America · 2024
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  15. The Yeast eIF2 Kinase Gcn2 Facilitates HApplied and environmental microbiology · 2021
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  17. DoesMicroorganisms · 2021
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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

7 authors at 3 institutions in 1 country.

Polly M FordyceDepartment of Biochemistry and Biophysics, University of California, San Francisco, CA 94158, USA.
David Pincus
Philipp Kimmig
Christopher S Nelson
Hana El-Samad
Peter Walter
Joseph L DeRisi
University of California, San Francisco · USHoward Hughes Medical Institute · USQB3 · US

Funding

Using Microfluidic Affinity Analysis to Probe Transcriptional RegulationK99GM099848 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FORDYCE, POLLY MORRELL · 2012 to 2013
$178k
Howard Hughes Medical InstituteNIGMS NIH HHS K99 GM099848
6 · The paper itself

Abstract

A quantitative understanding of how transcription factors interact with genomic target sites is crucial for reconstructing transcriptional networks in vivo. Here, we use Hac1, a well-characterized basic leucine zipper (bZIP) transcription factor involved in the unfolded protein response (UPR) as a model to investigate interactions between bZIP transcription factors and their target sites. During the UPR, the accumulation of unfolded proteins leads to unconventional splicing and subsequent translation of HAC1 mRNA, followed by transcription of UPR target genes. Initial candidate-based approaches identified a canonical cis-acting unfolded protein response element (UPRE-1) within target gene promoters; however, subsequent studies identified a large set of Hac1 target genes lacking this UPRE-1 and containing a different motif (UPRE-2). Using a combination of unbiased and directed microfluidic DNA binding assays, we established that Hac1 binds in two distinct modes: (i) to short (6-7 bp) UPRE-2-like motifs and (ii) to significantly longer (11-13 bp) extended UPRE-1-like motifs. Using a genetic screen, we demonstrate that a region of extended homology N-terminal to the basic DNA binding domain is required for this dual site recognition. These results establish Hac1 as the first bZIP transcription factor known to adopt more than one binding mode and unify previously conflicting and discrepant observations of Hac1 function into a cohesive model of UPR target gene activation. Our results also suggest that even structurally simple transcription factors can recognize multiple divergent target sites of very different lengths, potentially enriching their downstream target repertoire.

Indexed as

Alternative SplicingBase PairingBase SequenceBasic-Leucine Zipper Transcription FactorsBinding SitesDNAGenomeMicrofluidic Analytical TechniquesMolecular Sequence DataMutant ProteinsMutationNucleotide MotifsNucleotidesPosition-Specific Scoring MatricesProtein BindingProtein Structure, TertiaryBasic-Leucine Zipper Transcription FactorsDNAHAC1 protein, S cerevisiaeMutant ProteinsNucleotidesRepressor ProteinsRNA, MessengerSaccharomyces cerevisiae Proteins

Identifiers

PMID23054834
PMCPMC3494901
OpenAlexW2170942986

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.