Evidence map›Paper›PMID 22550178›Full record

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

Role of CCCTC binding factor (CTCF) and cohesin in the generation of single-cell diversity of protocadherin-α gene expression.

Kevin Monahan, Noam D Rudnick, Polina D Kehayova, Florencia Pauli, Kimberly M Newberry, Richard M Myers, Tom Maniatis

Open access · hybridAbstract 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 86 papers.

0numbers the graph read from it
0cells of the map it votes in
86citing papers in PubMed
7.4field-weighted citation impact, top 2% 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

86 citing papers in PubMed, 165 citations in OpenAlex.

  1. WAVE2 and REST/NRSF Regulate Clustered Gene Expression by Maintaining Heterochromatin Organization.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
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26 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 1 country.

Kevin MonahanDepartment of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA.
Noam D Rudnick
Polina D Kehayova
Florencia Pauli
Kimberly M Newberry
Richard M Myers
Tom Maniatis
Columbia University · USHudsonAlpha Institute for Biotechnology · USHarvard University · US

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM007367 · NIGMS · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI REINER, STEVEN L · 1985 to 2021
$25.1M
Protocadherin Gene Expression and FunctionR01NS043915 · NINDS · HARVARD UNIVERSITY · PI MANIATIS, THOMAS P · 2002 to 2011
$6.5M
NINDS NIH HHS R01 NS043915NINDS NIH HHS R01NS043915
6 · The paper itself

Abstract

Extraordinary single-cell diversity is generated in the vertebrate nervous system by the combinatorial expression of the clustered protocadherin genes (Pcdhα, -β, and -γ). This diversity is generated by a combination of stochastic promoter choice and alternative pre-mRNA splicing. Here we show that both the insulator-binding protein CTCF and the cohesin complex subunit Rad21 bind to two highly conserved DNA sequences, the first within and the second downstream of transcriptionally active Pcdhα promoters. Both CTCF and Rad21 bind to these sites in vitro and in vivo, this binding directly correlates with alternative isoform expression, and knocking down CTCF expression reduces alternative isoform expression. Remarkably, a similarly spaced pair of CTCF/Rad21 binding sites was identified within a distant enhancer element (HS5-1), which is required for normal levels of alternative isoform expression. We also identify an additional, unique regulatory role for cohesin, as Rad21 binds to another enhancer (HS7) independently of CTCF, and knockdown of Rad21 reduces expression of the constitutive, biallelically expressed Pcdhα isoforms αc1 and αc2. We propose that CTCF and the cohesin complex initiate and maintain Pcdhα promoter choice by mediating interactions between Pcdhα promoters and enhancers.

Indexed as

Alternative SplicingAnimalsBase SequenceCadherinsCCCTC-Binding FactorCell Cycle ProteinsCell LineChromatin ImmunoprecipitationChromosomal Proteins, Non-HistoneCohesinsDNA-Binding ProteinsElectrophoretic Mobility Shift AssayEnhancer Elements, GeneticGene Expression RegulationGene Knockdown TechniquesHumansCadherinsCCCTC-Binding FactorCell Cycle ProteinsChromosomal Proteins, Non-HistoneCohesinsCTCF protein, humanCtcf protein, mouseDNA-Binding ProteinsNuclear ProteinsPhosphoproteinsProtein IsoformsRad21 protein, mouseRepressor ProteinsRNA, Small Interfering

Identifiers

PMID22550178
PMCPMC3384188
OpenAlexW2005611301

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.