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Series GSE201519 Query DataSets for GSE201519
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)
GSM6065972 AJ1_1
GSM6065973 AJ1_2
GSM6065974 AJ1_3
BioProject PRJNA832123

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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
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Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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