Evidence map›Paper›PMID 28621576›Full record

ArticleEpigenetics2018

Tethering of Lsh at the Oct4 locus promotes gene repression associated with epigenetic changes.

Jianke Ren, Nathaniel A Hathaway, Gerald R Crabtree, Kathrin Muegge

Open access · bronzeAbstract read
In one paragraph

Article in Epigenetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
0.8field-weighted citation impact, top 29% 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

11 citing papers in PubMed, 11 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Review
  5. Review
  6. CRL4Cell death and differentiation · 2021
    Article
  7. Article
  8. Article
  9. 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

4 authors at 4 institutions in 1 country.

Jianke Rena Mouse Cancer Genetics Program , Center for Cancer Research, National Cancer Institute , Frederick , MD , USA.
Nathaniel A Hathawayb Division of Chemical Biology and Medicinal Chemistry, Center for Integrative Chemical Biology and Drug Discovery , UNC Eshelman School of Pharmacy , Chapel Hill , NC , USA.
Gerald R Crabtreec Departments of Pathology and Developmental Biology , Stanford University School of Medicine, Howard Hughes Medical Institute , CA , USA.
Kathrin Mueggea Mouse Cancer Genetics Program , Center for Cancer Research, National Cancer Institute , Frederick , MD , USA.
Center for Cancer Research · USNational Cancer Institute · USStanford University · USUniversity of North Carolina at Chapel Hill · US

Funding

Virology Research Program (Program 4)P30CA016086 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Deborah F. Tate · 1985 to 2026
$201.5M
Epigenetic control during embryogenesisZIABC010014 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI MUEGGE, KATHRIN · 2009 to 2025
$18.1M
ATP-Dependent Chromatin Remodeling in Human MalignancyR01CA163915 · NCI · STANFORD UNIVERSITY · PI Gerald R. Crabtree · 2012 to 2026
$5.4M
CCR NIH HHS HHSN261200800001CNCI NIH HHS HHSN261200800001ENCI NIH HHS P30 CA016086NCI NIH HHS R01 CA163915
6 · The paper itself

Abstract

Lsh is a chromatin remodeling factor that regulates DNA methylation and chromatin function in mammals. The dynamics of these chromatin changes and whether they are directly controlled by Lsh remain unclear. To understand the molecular mechanisms of Lsh chromatin controlled regulation of gene expression, we established a tethering system that recruits a Gal4-Lsh fusion protein to an engineered Oct4 locus through Gal4 binding sites in murine embryonic stem (ES) cells. We examined the molecular epigenetic events induced by Lsh binding including: histone modification, DNA methylation and chromatin accessibility to determine nucleosome occupancy before and after embryonic stem cell differentiation. Our results indicate that Lsh assists gene repression upon binding to the Oct4 promoter region. Furthermore, we detected less chromatin accessibility and reduced active histone modifications at the tethered site in undifferentiated ES, while GFP reporter gene expression and DNA methylation patterns remained unchanged at this stage. Upon differentiation, association of Lsh promotes transcriptional repression of the reporter gene accompanied by the increase of repressive histone marks and a gain of DNA methylation at distal and proximal Oct4 enhancer sites. Taken together, this approach allowed us to examine Lsh mediated epigenetic regulation as a dynamic process and revealed chromatin accessibility changes as the primary consequence of Lsh function.

Indexed as

Chromatin Assembly and DisassemblyEpigenesis, GeneticAnimalsCells, CulturedDNA HelicasesHistone CodeMiceNucleosomesOctamer Transcription Factor-3Promoter Regions, GeneticDNA Helicaseslymphoid specific helicase, mouseNucleosomesOctamer Transcription Factor-3Pou5f1 protein, mouseDNA methylationepigeneticshistone modificationsnucleosome occupancytethering

Identifiers

PMID28621576
PMCPMC5873361
OpenAlexW2625582418

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.