Evidence map›Paper›PMID 17640912›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2007

Pioneer factor interactions and unmethylated CpG dinucleotides mark silent tissue-specific enhancers in embryonic stem cells.

Jian Xu, Scott D Pope, Ali R Jazirehi, Joanne L Attema, Peter Papathanasiou, Jason A Watts, Kenneth S Zaret, Irving L Weissman, Stephen T Smale

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.

0numbers the graph read from it
0cells of the map it votes in
69citing papers in PubMed
3.4field-weighted citation impact, top 7% 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

69 citing papers in PubMed, 112 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. 1α,25(OH)Journal for immunotherapy of cancer · 2022
    Article
  5. Loss of Monoallelic Expression ofFrontiers in genetics · 2022
    Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. PBX1 as Pioneer Factor: A Case Still Open.Frontiers in cell and developmental biology · 2017
    Review
  17. Genetic and Epigenetic Regulation of PD-1 Expression.Journal of immunology (Baltimore, Md. : 1950) · 2016
    Review
  18. Article
  19. Article
  20. Article

9 more citing papers are in PubMed but not listed here.

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

9 authors at 4 institutions in 1 country.

Jian XuHoward Hughes Medical Institute, Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA.
Scott D Pope
Ali R Jazirehi
Joanne L Attema
Peter Papathanasiou
Jason A Watts
Kenneth S Zaret
Irving L Weissman
Stephen T Smale
Stanford University · USUniversity of California, Los Angeles · USFox Chase Cancer Center · USHoward Hughes Medical Institute · US

Funding

MULTIDISCIPLINARY TRAINING IN MICROBIAL PATHOGENESIST32AI007323 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Peter John Bradley · 1988 to 2026
$8.6M
STEM CELL DETRMINATION GENES IN HSC AND HEMATOLYMPHOID CELLS IN MICEP01DK053074 · NIDDK · STANFORD UNIVERSITY · PI CLARKE, MICHAEL F · 1997 to 2007
$8.3M
HIGHER ORDER PROTEIN-DNA COMPLEXES IN GENE REGULATIONR01GM047903 · NIGMS · INSTITUTE FOR CANCER RESEARCH · PI ZARET, KENNETH S. · 1994 to 2005
$1.4M
Predoctoral Fellowship for Minority StudentsF31GM066367 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI WATTS, JASON · 2002 to 2006
$231k
NIAID NIH HHS T32 AI007323NIAID NIH HHS T32 AI07323NIDDK NIH HHS P01 DK053074NIDDK NIH HHS P01 DK53074NIGMS NIH HHS F31 GM066367NIGMS NIH HHS GM066367-05NIGMS NIH HHS R01 GM047903NIGMS NIH HHS R01 GM47903
6 · The paper itself

Abstract

Recent studies have suggested that, in ES cells, inactive genes encoding early developmental regulators possess bivalent histone modification domains and are therefore poised for activation. However, bivalent domains were not observed at typical tissue-specific genes. Here, we show that windows of unmethylated CpG dinucleotides and putative pioneer factor interactions mark enhancers for at least some tissue-specific genes in ES cells. The unmethylated windows expand in cells that express the gene and contract, disappear, or remain unchanged in nonexpressing tissues. However, in ES cells, they do not always coincide with common histone modifications. Genomic footprinting and chromatin immunoprecipitation demonstrated that transcription factor binding underlies the unmethylated windows at enhancers for the Ptcra and Alb1 genes. After stable integration of premethylated Ptcra enhancer constructs into the ES cell genome, the unmethylated windows readily appeared. In contrast, the premethylated constructs remained fully methylated and silent after introduction into Ptcra-expressing thymocytes. These findings provide initial functional support for a model in which pioneer factor interactions in ES cells promote the assembly of a chromatin structure that is permissive for subsequent activation, and in which differentiated tissues lack the machinery required for gene activation when these ES cell marks are absent. The enhancer marks may therefore represent important features of the pluripotent state.

Indexed as

Gene SilencingAlbuminsAnimalsCell LineCpG IslandsDNA MethylationEmbryonic Stem CellsEnhancer Elements, GeneticGenetic MarkersHematopoiesisHistonesHumansInterleukin-12Membrane GlycoproteinsMiceMolecular Sequence DataAlbuminsGenetic MarkersHistonesInterleukin-12Membrane GlycoproteinsNucleotidespre-T cell receptor alphaReceptors, Antigen, T-Cell, alpha-betaTranscription Factors

Identifiers

PMID17640912
PMCPMC1941477
OpenAlexW2015428618

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.