Muscular Dystrophy, Facioscapulohumeral
|
0.600 |
AlteredExpression
|
disease |
BEFREE |
In vitro experiments demonstrate that clinically advanced p38 inhibitors suppress <i>DUX4</i> expression in FSHD type 1 and 2 myoblasts and differentiating myocytes in vitro with exquisite potency.
|
31189728 |
2019 |
Muscular Dystrophy, Facioscapulohumeral
|
0.600 |
AlteredExpression
|
disease |
BEFREE |
FSHD is generally associated with the contraction of D4Z4 macrosatellite repeats on 4q35 chromosome or mutations in SMCHD1, which are responsible of the toxic expression of DUX4 in muscle tissue.
|
30911870 |
2019 |
Muscular Dystrophy, Facioscapulohumeral
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
Facioscapulohumeral muscular dystrophy (FSHD) is a prevalent, incurable myopathy, linked to epigenetic derepression of D4Z4 repeats on chromosome 4q, leading to ectopic DUX4 expression.
|
30462217 |
2019 |
Muscular Dystrophy, Facioscapulohumeral
|
0.600 |
Biomarker
|
disease |
BEFREE |
FSHD xenografts express DUX4 and DUX4 downstream targets, retain the 4q35 epigenetic signature of their original donors, and express a novel protein biomarker of FSHD, SLC34A2.
|
31306642 |
2019 |
Muscular Dystrophy, Facioscapulohumeral
|
0.600 |
Biomarker
|
disease |
BEFREE |
When misexpressed in FSHD skeletal muscle, the DUX4 program leads to accumulated muscle pathology.
|
31018108 |
2019 |
Muscular Dystrophy, Facioscapulohumeral
|
0.600 |
AlteredExpression
|
disease |
BEFREE |
We find that FSHD and BAMS patient's cells carrying SMCHD1 mutations are both permissive for DUX4 expression, a transcription factor whose regulation has been proposed as the main trigger for FSHD.
|
30698748 |
2019 |
Muscular Dystrophy, Facioscapulohumeral
|
0.600 |
AlteredExpression
|
disease |
BEFREE |
We describe the activity of a new spirocyclic EP300/CBP inhibitor, iP300w, which inhibits the cytotoxicity of the DUX4 protein and reverses the overexpression of most DUX4 target genes, in engineered cell lines and FSHD myoblasts, as well as in an FSHD animal model.
|
31535023 |
2019 |
Muscular Dystrophy, Facioscapulohumeral
|
0.600 |
Biomarker
|
disease |
BEFREE |
Importantly, PAX7 target gene repression is a significant biomarker in the majority of FSHD cells that are DUX4 target gene negative, and on which the DUX4 biomarker is indiscriminate.
|
31067297 |
2019 |
Muscular Dystrophy, Facioscapulohumeral
|
0.600 |
AlteredExpression
|
disease |
BEFREE |
We furthermore generated an FSHD cellular progression model, reflecting both the early burst-like DUX4 expression as well as the downstream activation of various FSHD-associated pathways, which allowed us to correlate DUX4 expression signature dynamics with that of regulatory complexes, thereby facilitating the prioritization of epigenetic targets for DUX4 silencing.
|
30445587 |
2019 |
Muscular Dystrophy, Facioscapulohumeral
|
0.600 |
Biomarker
|
disease |
BEFREE |
Our results provide a resource for the FSHD community and illustrate the importance of post-transcriptional processes in DUX4-induced pathology.
|
30644821 |
2019 |
Muscular Dystrophy, Facioscapulohumeral
|
0.600 |
AlteredExpression
|
disease |
BEFREE |
These results support the use of MRI to identify FSHD muscles most likely to have active disease and higher levels of DUX4 target gene expression and might be useful in early phase therapeutic trials to demonstrate target engagement in therapies aiming to suppress DUX4 expression.
|
30312408 |
2019 |
Muscular Dystrophy, Facioscapulohumeral
|
0.600 |
AlteredExpression
|
disease |
BEFREE |
In this study, we expand upon our previously established injection model of DUX4 misexpression in zebrafish and describe a DUX4-inducible transgenic zebrafish model that better recapitulates the expression pattern and late onset phenotype characteristic of FSHD patients.
|
30307508 |
2019 |
Muscular Dystrophy, Facioscapulohumeral
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
Facioscapulohumeral muscular dystrophy (FSHD) is a dominantly-inherited progressive muscular dystrophy caused by de-repression of the DUX4 gene, which causes disease by a toxic-gain-of-function.
|
31506080 |
2019 |
Muscular Dystrophy, Facioscapulohumeral
|
0.600 |
AlteredExpression
|
disease |
BEFREE |
Mis-expression of DUX4 in skeletal muscle, however, is toxic and causes facioscapulohumeral muscular dystrophy (FSHD).
|
31630170 |
2019 |
Muscular Dystrophy, Facioscapulohumeral
|
0.600 |
AlteredExpression
|
disease |
BEFREE |
Critically, 4-methylumbelliferone does not disrupt DUX4-C1QBP binding and has only a limited effect on DUX4 transcriptional activity, establishing that HA signaling has a central function in pathology and is a target for FSHD therapeutics.
|
31844661 |
2019 |
Muscular Dystrophy, Facioscapulohumeral
|
0.600 |
Biomarker
|
disease |
BEFREE |
Our work provides a framework for understanding the endogenous function of DUX4 and its role in FSHD and cancer.
|
30540931 |
2018 |
Muscular Dystrophy, Facioscapulohumeral
|
0.600 |
Biomarker
|
disease |
BEFREE |
Loss of silencing of the DUX4 gene on chromosome 4 causes facioscapulohumeral muscular dystrophy.
|
30446688 |
2018 |
Muscular Dystrophy, Facioscapulohumeral
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
Facioscapulohumeral muscular dystrophy, known in genetic forms FSHD1 and FSHD2, is associated with D4Z4 repeat array chromatin relaxation and somatic derepression of DUX4 located in D4Z4.
|
30281091 |
2018 |
Muscular Dystrophy, Facioscapulohumeral
|
0.600 |
Biomarker
|
disease |
BEFREE |
Although DUX4 silencing normalizes the FSHD atrophic myotube phenotype, this is not the case for the disorganized phenotype.
|
29329560 |
2018 |
Muscular Dystrophy, Facioscapulohumeral
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
Individuals with facioscapulohumeral muscular dystrophy (FSHD) have a partial failure of somatic DUX4 repression resulting in the presence of DUX4 protein in sporadic muscle nuclei.
|
29281018 |
2018 |
Muscular Dystrophy, Facioscapulohumeral
|
0.600 |
Biomarker
|
disease |
BEFREE |
Reasoning that DUX4-fl activators might represent useful targets for small molecule inhibition, we performed a highly targeted, candidate-based screen of epigenetic regulators in primary FSHD myocytes.
|
29759937 |
2018 |
Muscular Dystrophy, Facioscapulohumeral
|
0.600 |
AlteredExpression
|
disease |
BEFREE |
FSHD is caused by expression of DUX4, a retrogene located on the D4Z4 macrosatellite repeat array on chromosome 4q35, a gene expressed in the germline but typically repressed in somatic tissue.
|
30361930 |
2018 |
Muscular Dystrophy, Facioscapulohumeral
|
0.600 |
Biomarker
|
disease |
BEFREE |
Functional domains of the FSHD-associated DUX4 protein.
|
29618456 |
2018 |
Muscular Dystrophy, Facioscapulohumeral
|
0.600 |
AlteredExpression
|
disease |
BEFREE |
Together, these findings identify NuRD and CAF-1 as mediators of DUX4 chromatin repression and suggest a mechanism for the amplification of DUX4 expression in FSHD muscle cells.
|
29533181 |
2018 |
Muscular Dystrophy, Facioscapulohumeral
|
0.600 |
AlteredExpression
|
disease |
BEFREE |
Facioscapulohumeral muscular dystrophy is caused by incomplete repression of the transcription factor DUX4 in skeletal muscle as a consequence of D4Z4 macrosatellite repeat contraction in chromosome 4q35 (FSHD1) or variants in genes encoding D4Z4 chromatin repressors (FSHD2).
|
29162933 |
2018 |