 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Sep 14, 2022 |
| Title |
Differential DNA Methylation Drives Allelic Architecture for Grb10-Ddc Locus in the Developing Heart |
| Organism |
Mus musculus |
| Experiment type |
Other
|
| Summary |
While it is understood that the genome is organized into large domains, little is known about cell-type specific interactions at individual loci in mammalian development. Imprinted loci represent a compelling feature of chromatin conformation, illustrating how genes are controlled in local domains to drive parental-specific transcriptional programs important for growth: a clear example being the imprinted Grb10-Ddc locus. Using hybrid mouse crosses and genetic engineering, we uncovered an insulator at Grb10 that is tissue-specific and dynamically controlled by DNA methylation. Insulator CBR2.3 acquires paternal-specific hypomethylation post-implantation, assembling a higher-order structure on the paternal chromosome. Deletion of paternal CBR2.3 converts the chromatin domain to the maternal configuration, redirecting Grb10-Ddc enhancer function, resulting in major cardiac phenotypes. We conclude that CBR2.3 functions as a shared, paternal and tissue-specific insulator for Grb10-Ddc expression in heart, contributing to fundamentally different chromosomal conformations that impact enhancer activity in vivo.
|
| |
|
| Overall design |
Capture-C on F1 hybrid hearts derived from reciprocal crosses between C57BL/6 (B6) mice and animals homozygous for the Japanese Fancy (JF1/Ms) strain.
|
| |
|
| Contributor(s) |
Juan A, Foong YH, Thorvaldsen JL, Leu N, Lan Y, Rurik J, Li L, Rosier C, Epstein JA, Bartolomei MS |
| Citation(s) |
36108632 |
| |
| Submission date |
Apr 26, 2022 |
| Last update date |
Dec 14, 2022 |
| Contact name |
Yemin Lan |
| Organization name |
University of Pennsylvania
|
| Street address |
3400 Civic Center Blvd
|
| City |
Philadelphia |
| State/province |
PA |
| ZIP/Postal code |
19104 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
|
| Samples (16)
|
|
| Relations |
| BioProject |
PRJNA832123 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE201519_RAW.tar |
238.8 Mb |
(http)(custom) |
TAR (of TAR) |
| GSE201519_loops.tar.gz |
541.9 Kb |
(ftp)(http) |
TAR |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
|
|
|
|
 |
Less...
More...