Evidence map›Paper›PMID 22600741›Full record

ArticleNucleic acids research2012

Repetitive elements and enforced transcriptional repression co-operate to enhance DNA methylation spreading into a promoter CpG-island.

Yan Zhang, Jingmin Shu, Jiali Si, Lanlan Shen, Marcos R H Estecio, Jean-Pierre J Issa

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
2.6field-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

16 citing papers in PubMed, 32 citations in OpenAlex.

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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

6 authors at 5 institutions in 1 country.

Yan ZhangDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
Jingmin Shu
Jiali Si
Lanlan Shen
Marcos R H Estecio
Jean-Pierre J Issa
The University of Texas Health Science Center at Houston · USBaylor College of Medicine · USTemple University · USThe Graduate Center, CUNY · USThe University of Texas MD Anderson Cancer Center · US

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8M
University of Texas M.D. Anderson Cancer SPORE-LeukemiaP50CA100632 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI KONOPLEVA, MARINA Y · 2003 to 2023
$43.7M
DNA Methylation in Colon Cancer MetastasisR01CA098006 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI ISSA, JEAN-PIERRE J. · 2004 to 2008
$1.4M
NCI NIH HHS CA098006NCI NIH HHS CA100632NCI NIH HHS CA16672NCI NIH HHS P30 CA016672
6 · The paper itself

Abstract

Repression of many tumor suppressor genes in cancer is concurrent with aberrantly increased DNA methylation levels at promoter CpG islands (CGIs). About one-fourth of empirically defined human promoters are surrounded by or contain clustered repetitive elements. It was previously observed that a sharp transition of methylation exists between highly methylated repetitive elements and unmethylated promoter-CGIs in normal tissues. The factors that lead to aberrant CGI hypermethylation in cancer remain poorly understood. Here, we established a site-specific integration system with enforced local transcriptional repression in colorectal cancer cells and monitored the occurrence of initial de novo methylation at specific CG sites adjacent to the CGI of the INSL6 promoter, which could be accelerated by binding a KRAB-containing transcriptional factor. Additional repetitive elements from P16 and RIL (PDLIM4), if situated adjacent to the promoter of INSL6, could confer DNA methylation spreading into the CGI particularly in the setting of KRAB-factor binding. However, a repressive chromatin alone was not sufficient to initiate DNA methylation, which required specific DNA sequences and was integration-site (and/or cell-line) specific. Overall, these results demonstrate a requirement for specific DNA sequences to trigger de novo DNA methylation, and repetitive elements as cis-regulatory factors to cooperate with advanced transcriptional repression in promoting methylation spreading.

Indexed as

CpG IslandsDNA MethylationGene SilencingPromoter Regions, GeneticRepetitive Sequences, Nucleic AcidTranscription, GeneticCell Line, TumorChromatinDNAHumansIntercellular Signaling Peptides and ProteinsTransgenesChromatinDNAIntercellular Signaling Peptides and Proteins

Identifiers

PMID22600741
PMCPMC3424568
OpenAlexW2148080736

What OpenQuestion holds

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LicenceCC BY-NC
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.