Evidence map›Paper›PMID 25184003›Full record

ArticleEpigenetics & chromatin2014

Targeted gene suppression by inducing de novo DNA methylation in the gene promoter.

Ai-Niu Ma, Hong Wang, Rui Guo, Yong-Xiang Wang, Wei Li, Jiuwei Cui, Guanjun Wang, Andrew R Hoffman, Ji-Fan Hu

Open access · goldAbstract read
In one paragraph

Article in Epigenetics & chromatin, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.1field-weighted citation impact, top 22% 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

12 citing papers in PubMed, 18 citations in OpenAlex.

  1. Article
  2. Article
  3. KRAB-Induced Heterochromatin Effectively SilencesInternational journal of molecular sciences · 2020
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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

9 authors at 4 institutions in 2 countries.

Ai-Niu Ma *King's Lab, Shanghai Jiao Tong University School of Pharmacy, 800 Dongchuan Road, Shanghai 200240, China.
Hong Wang *King's Lab, Shanghai Jiao Tong University School of Pharmacy, 800 Dongchuan Road, Shanghai 200240, China.
Rui GuoKing's Lab, Shanghai Jiao Tong University School of Pharmacy, 800 Dongchuan Road, Shanghai 200240, China.
Yong-Xiang WangKing's Lab, Shanghai Jiao Tong University School of Pharmacy, 800 Dongchuan Road, Shanghai 200240, China.
Wei LiStem Cell and Cancer Center, First Affiliated Hospital, Jilin University, 519 Dongminzhu Blvd, Changchun 130021, China.
Jiuwei CuiStem Cell and Cancer Center, First Affiliated Hospital, Jilin University, 519 Dongminzhu Blvd, Changchun 130021, China.
Guanjun WangStem Cell and Cancer Center, First Affiliated Hospital, Jilin University, 519 Dongminzhu Blvd, Changchun 130021, China.
Andrew R HoffmanStanford University Medical School, VA Palo Alto Health Care System, 3801 Miranda Avenue, Palo Alto, CA 94304, USA.
Ji-Fan HuStem Cell and Cancer Center, First Affiliated Hospital, Jilin University, 519 Dongminzhu Blvd, Changchun 130021, China.
Shanghai Jiao Tong University · CNFirst Hospital of Jilin University · CNJilin University · CNStanford University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundTargeted gene silencing is an important approach in both drug development and basic research. However, the selection of a potent suppressor has become a significant hurdle to implementing maximal gene inhibition for this approach. We attempted to construct a 'super suppressor' by combining the activities of two suppressors that function through distinct epigenetic mechanisms.

resultsGene targeting vectors were constructed by fusing a GAL4 DNA-binding domain with a epigenetic suppressor, including CpG DNA methylase Sss1, histone H3 lysine 27 methylase vSET domain, and Kruppel-associated suppression box (KRAB). We found that both Sss1 and KRAB suppressors significantly inhibited the expression of luciferase and copGFP reporter genes. However, the histone H3 lysine 27 methylase vSET did not show significant suppression in this system. Constructs containing both Sss1 and KRAB showed better inhibition than either one alone. In addition, we show that KRAB suppressed gene expression by altering the histone code, but not DNA methylation in the gene promoter. Sss1, on the other hand, not only induced de novo DNA methylation and recruited Heterochromatin Protein 1 (HP1a), but also increased H3K27 and H3K9 methylation in the promoter.

conclusionsEpigenetic studies can provide useful data for the selection of suppressors in constructing therapeutic vectors for targeted gene silencing.

Indexed as

DNA methylationEpigeneticsGene expressionGene suppressionH3K27 methylationHistone code

Identifiers

PMID25184003
PMCPMC4150861
OpenAlexW2095718399

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.