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| Status |
Public on Sep 25, 2017 |
| Title |
Loss of imprinting mutations define both distinct and overlapping roles for misexpression of IGF2 and H19 lncRNA |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Imprinted genes occur in discrete clusters that are coordinately regulated by shared DNA elements. H19 and Igf2 are linked imprinted genes that play critical roles in development. Loss of imprinting at the IGF2/H19 locus is associated with Beckwith Wiedemann Syndrome (BWS). Here we use comprehensive genetic and genomic analyses to follow muscle development in a mouse model of BWS to dissect the separate and shared roles for Igf2 and H19 in the disease phenotype. We show that LOI results in defects in muscle differentiation and hypertrophy and we identify primary downstream targets of Igf2 (MAPK signaling) and of H19 (AKT/mTOR signaling). Moreover, we demonstrate instances where H19 and Igf2 misexpression work separately, cooperatively, and also antagonistically to establish the disease phenotype. This study underscores the fact that LOI phenotypes are multigenic and complex interactions contribute to disease outcomes.
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| Overall design |
Total of 13 samples analyzed; RNA-Seq samples from 2 genotypes: wild type and dICR/dICR, 2 cell types: myoblasts and myotubes, 2-3 replicates each.
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| Contributor(s) |
Mitra A, Park KS, Kim K, Pfeifer K |
| Citation(s) |
29244185 |
| Submission date |
Oct 24, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Apratim Mitra |
| E-mail(s) |
apratim.mitra@nih.gov
|
| Phone |
3014020676
|
| Organization name |
NICHD
|
| Department |
Division of Developmental Biology
|
| Lab |
Section on Genomic Imprinting
|
| Street address |
6 Center Dr Building 6B Room 2B206
|
| City |
Bethesda |
| State/province |
MD |
| ZIP/Postal code |
20892 |
| Country |
USA |
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| Platforms (2) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
| GPL15907 |
AB 5500xl Genetic Analyzer (Mus musculus) |
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| Samples (13)
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| Relations |
| BioProject |
PRJNA350351 |
| SRA |
SRP092014 |
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