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Histone methylation levels correlate with TGFBIp and extracellular matrix gene expression in normal and granular corneal dystrophy type 2 corneal fibroblasts

Overview of attention for article published in BMC Medical Genomics, November 2015
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Title
Histone methylation levels correlate with TGFBIp and extracellular matrix gene expression in normal and granular corneal dystrophy type 2 corneal fibroblasts
Published in
BMC Medical Genomics, November 2015
DOI 10.1186/s12920-015-0151-8
Pubmed ID
Authors

Yong-Sun Maeng, Ga-Hyun Lee, Seung-Il Choi, Kyu Seo Kim, Eung Kweon Kim

Abstract

TGFβ1-induced expression of transforming growth factor β-induced protein (TGFBIp) and extracellular matrix (ECM) genes plays a major role in the development of granular corneal dystrophy type 2 (GCD2: also called Avellino corneal dystrophy). Although some key transcription factors are known, the epigenetic mechanisms modulating TGFBIp and ECM expression remain unclear. We examined the role of chromatin markers such as histone H3 lysine methylation (H3Kme) in TGFβ1-induced TGFBIp and ECM gene expression in normal and GCD2-derived human corneal fibroblasts. Wild-type (n = 3), GCD2-heterozygous (n = 1), and GCD2-homozygous (n = 3) primary human corneal fibroblasts were harvested from human donors and patients prepared. Microarray and gene-expression profiling, Chromatin immunoprecipitation microarray analysis, and Methylated DNA isolation assay-assisted CpG microarrays was performed in Wild-type and GCD2-homozygous human cells. Transcription and extracellular-secretion levels of TGFBIp were high in normal cells compared with those in GCD2-derived cells and were related to H3K4me3 levels but not to DNA methylation over the TGFBI locus. TGFβ1 increased the expression of TGFBIp and the ECM-associated genes connective tissue growth factor, collagen-α2[Ι], and plasminogen activator inhibitor-1 in normal corneal fibroblasts. Increased levels of gene-activating markers (H3K4me1/3) and decreased levels of repressive markers (H3K27me3) at the promoters of those gene accompanied the changes in expression. TGFβ1 also increased recruitment of the H3K4 methyltransferase MLL1 and of SET7/9 and also the binding of Smad3 to the promoters. Knockdown of both MLL1 and SET7/9 significantly blocked the TGFβ1-induced gene expression and inhibited TGFβ1-induced changes in promoter H3K4me1/3 levels. Those effects were very weak, however, in GCD2-derived corneal fibroblasts. Taken together, the results show the functional role of H3K4me in TGFβ1-mediated TGFBIp and ECM gene expression in corneal fibroblasts. Pharmacologic and other therapies that regulate these modifications could have potential cornea-protective effects for granular corneal dystrophy.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 14 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 14 100%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 3 21%
Other 2 14%
Student > Ph. D. Student 2 14%
Student > Doctoral Student 1 7%
Student > Master 1 7%
Other 2 14%
Unknown 3 21%
Readers by discipline Count As %
Medicine and Dentistry 5 36%
Biochemistry, Genetics and Molecular Biology 4 29%
Agricultural and Biological Sciences 2 14%
Unknown 3 21%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 26 April 2016.
All research outputs
#13,450,206
of 22,832,057 outputs
Outputs from BMC Medical Genomics
#501
of 1,223 outputs
Outputs of similar age
#134,837
of 284,824 outputs
Outputs of similar age from BMC Medical Genomics
#13
of 23 outputs
Altmetric has tracked 22,832,057 research outputs across all sources so far. This one is in the 39th percentile – i.e., 39% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,223 research outputs from this source. They receive a mean Attention Score of 4.7. This one has gotten more attention than average, scoring higher than 56% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 284,824 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 51% of its contemporaries.
We're also able to compare this research output to 23 others from the same source and published within six weeks on either side of this one. This one is in the 43rd percentile – i.e., 43% of its contemporaries scored the same or lower than it.