Evidence map›Paper›PMID 36343842›Full record

ArticleJournal of structural biology2022

Structural basis for cell type specific DNA binding of C/EBPβ: The case of cell cycle inhibitor p15INK4b promoter.

George T Lountos, Scott Cherry, Joseph E Tropea, Alexander Wlodawer, Maria Miller

Open access · greenAbstract read
In one paragraph

Article in Journal of structural biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed, 1 pooled it
0.5field-weighted citation impact, top 38% 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

3 citing papers in PubMed, 1 synthesis or guideline pooled it, 6 citations in OpenAlex.

  1. Pooled it
  2. GermlineeLife · 2024
    Article
  3. GermlinebioRxiv : the preprint server for biology · 2024
    Article
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

5 authors at 2 institutions in 1 country.

George T LountosBasic Science Program, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA. Electronic address: lountosg@mail.nih.gov.
Scott CherryProtein Purification Core, Center for Structural Biology, National Cancer Institute, Frederick, MD 21702-1201, USA.
Joseph E TropeaProtein Purification Core, Center for Structural Biology, National Cancer Institute, Frederick, MD 21702-1201, USA.
Alexander WlodawerProtein Structure Section, Center for Structural Biology, National Cancer Institute, Frederick, MD 21702-1201 USA.
Maria MillerProtein Structure Section, Center for Structural Biology, National Cancer Institute, Frederick, MD 21702-1201 USA.
National Cancer Institute · USFrederick National Laboratory for Cancer Research · US

Funding

WORK ORDER 126643 B539 EXPAND IC SUITE75N91019D00024 · NIAID · LEIDOS BIOMEDICAL RESEARCH, INC. · PI BRISCOE, LYNN · 2019 to 2025
$3932.6M
Phase II SER-CAT Optimization: Acquisition of a next generation area detectorS10RR028976 · NCRR · UNIVERSITY OF GEORGIA · PI WANG, BI-CHENG · 2010 to 2010
$1.5M
Acquisition of a High Precision Micro Diffractometer to Support NIH funded Research at SER-CATS10OD027000 · OD · UNIVERSITY OF GEORGIA · PI ROSE, JOHN PATRICK · 2019 to 2019
$600k
Acquition of a microdiffractometer for SER-CATS10RR025528 · NCRR · UNIVERSITY OF GEORGIA · PI ROSE, JOHN PATRICK · 2009 to 2009
$414k
Intramural NIH HHS Z99 CA999999NCI NIH HHS 75N91019D00024NCRR NIH HHS S10 RR025528NCRR NIH HHS S10 RR028976NIH HHS S10 OD027000
6 · The paper itself

Abstract

C/EBPβ is a key regulator of numerous cellular processes, but it can also contribute to tumorigenesis and viral diseases. It binds to specific DNA sequences (C/EBP sites) and interacts with other transcription factors to control expression of multiple eukaryotic genes in a tissue and cell-type dependent manner. A body of evidence has established that cell-type-specific regulatory information is contained in the local DNA sequence of the binding motif. In human epithelial cells, C/EBPβ is an essential cofactor for TGFβ signaling in the case of Smad2/3/4 and FoxO-dependent induction of the cell cycle inhibitor, p15INK4b. In the TGFβ-responsive region 2 of the p15INK4b promoter, the Smad binding site is flanked by a C/EBP site, CTTAA•GAAAG, which differs from the canonical, palindromic ATTGC•GCAAT motif. The X-ray crystal structure of C/EBPβ bound to the p15INK4b promoter fragment shows how GCGC-to-AAGA substitution generates changes in the intermolecular interactions in the protein-DNA interface that enhances C/EBPβ binding specificity, limits possible epigenetic regulation of the promoter, and generates a DNA element with a unique pattern of methyl groups in the major groove. Significantly, CT/GA dinucleotides located at the 5'ends of the double stranded element maintain local narrowing of the DNA minor groove width that is necessary for DNA recognition. Our results suggest that C/EBPβ would accept all forms of modified cytosine in the context of the CpT site. This contrasts with the effect on the consensus motif, where C/EBPβ binding is modestly increased by cytosine methylation, but substantially decreased by hydroxymethylation.

Indexed as

CCAAT-Enhancer-Binding Protein-betaEpigenesis, GeneticCell CycleCytosineDNAHumansCCAAT-Enhancer-Binding Protein-betaCytosineDNABinding site specificityC/EBPβ-DNA interactionsDNA methylationDNA sequence motifDNA shape recognitionGenomic occupancy

Identifiers

PMID36343842
PMCPMC9909937
OpenAlexW4308193975

What OpenQuestion holds

Textmetadata
LicenceTDM
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.