Evidence map›Paper›PMID 11689684›Full record

ArticleMolecular and cellular biology2001

Methylation-mediated proviral silencing is associated with MeCP2 recruitment and localized histone H3 deacetylation.

M C Lorincz, D Schübeler, M Groudine

Open access · greenAbstract read
In one paragraph

Article in Molecular and cellular biology, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed
7.0field-weighted citation impact, top 3% 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

46 citing papers in PubMed, 98 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

3 authors at 1 institution in 2 countries.

M C LorinczDivision of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
D Schübeler
M Groudine
Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa · ZA

Funding

FUNCTION OF HUMAN &MOUSE B GLOBIN LOCUS CONTROL REGIONSR37DK044746 · NIDDK · FRED HUTCHINSON CANCER RESEARCH CENTER · PI GROUDINE, MARK T · 1997 to 2016
$12.3M
FACS-BASED SCREEN FOR TRANS-SENSING IN MAMMALIAN CELLSF32GM019767 · NIGMS · FRED HUTCHINSON CANCER RESEARCH CENTER · PI LORINCZ, MATTHEW C · 1999 to 2001
$80k
FUNCTION OF THE HUMAN B-GLOBIN LOCUS CONTROL REGION-LCRR01DK044746 · NIDDK · FRED HUTCHINSON CANCER RESEARCH CENTER · PI GROUDINE, MARK T · 1992 to 1996
–
MAINTENANCE AND REGULATION OF GLOBIN GENE EXPRESSIONR01HL057620 · NHLBI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI GROUDINE, MARK T · 1996 to 1999
–
NHLBI NIH HHS HL57620NIDDK NIH HHS DK44746NIDDK NIH HHS R37 DK044746NIGMS NIH HHS F32 GM019767NIGMS NIH HHS GM 19767/01
6 · The paper itself

Abstract

The majority of 5-methylcytosine in mammalian DNA resides in endogenous transposable elements and is associated with the transcriptional silencing of these parasitic elements. Methylation also plays an important role in the silencing of exogenous retroviruses. One of the difficulties inherent in the study of proviral silencing is that the sites in which proviruses randomly integrate influence the probability of de novo methylation and expression. In order to compare methylated and unmethylated proviruses at the same genomic site, we used a recombinase-based targeting approach to introduce an in vitro methylated or unmethylated Moloney murine leukemia-based provirus in MEL cells. The methylated and unmethylated states are maintained in vivo, with the exception of the initially methylated proviral enhancer, which becomes demethylated in vivo. Although the enhancer is unmethylated and remodeled, the methylated provirus is transcriptionally silent. To further analyze the repressed state, histone acetylation status was determined by chromatin immunoprecipitation (ChIP) analyses, which revealed that localized histone H3 but not histone H4 hyperacetylation is inversely correlated with proviral methylation density. Since members of the methyl-CpG binding domain (MBD) family of proteins recruit histone deacetylase activity, these proteins may play a role in proviral repression. Interestingly, only MBD3 and MeCP2 are expressed in MEL cells. ChIPs with antibodies specific for these proteins revealed that only MeCP2 associates with the provirus in a methylation-dependent manner. Taken together, our results suggest that MeCP2 recruitment to a methylated provirus is sufficient for transcriptional silencing, despite the presence of a remodeled enhancer.

Indexed as

Chromosomal Proteins, Non-HistoneDNA MethylationAnimalsBinding SitesCell LineClone CellsCpG IslandsDNA-Binding ProteinsDNA, ViralEndogenous RetrovirusesGene SilencingGene TargetingHistone DeacetylasesHistonesIntegrasesMethyl-CpG-Binding Protein 2Chromosomal Proteins, Non-HistoneCre recombinaseDNA-Binding ProteinsDNA, ViralHistone DeacetylasesHistonesIntegrasesMecp2 protein, mouseMethyl-CpG-Binding Protein 2Repressor ProteinsViral Proteins

Identifiers

PMID11689684
PMCPMC99960
OpenAlexW2043207143

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.