 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Aug 07, 2023 |
| Title |
Allelic chromatin structure primes imprinted expression of Kcnk9 during neurogenesis |
| Organism |
Mus musculus |
| Experiment type |
Other
|
| Summary |
Differences in chromatin state inherited from the parental gametes influence the regulation of maternal and paternal alleles in offspring. This phenomenon, known as genomic imprinting, results in genes preferentially transcribed from one parental allele. While local epigenetic factors such as DNA methylation are known to be important for the establishment of imprinted gene expression, less is known about the mechanisms by which differentially methylated regions (DMRs) lead to differences in allelic expression across broad stretches of chromatin. Allele-specific higher-order chromatin structure has been observed at multiple imprinted loci, consistent with the observation of allelic binding of the chromatin-organizing factor CTCF at multiple DMRs. However, whether allelic chromatin structure impacts allelic gene expression is not known for most imprinted loci. Here we characterize the mechanisms underlying brain-specific imprinted expression of the Peg13-Kcnk9 locus, an imprinted region associated with intellectual disability. We performed region capture Hi-C on mouse brain from reciprocal hybrid crosses and found imprinted higher-order chromatin structure caused by the allelic binding of CTCF to the Peg13 DMR. Using an in vitro neuron differentiation system, we show that on the maternal allele, an enhancer-promoter contact formed early in development primes the brain-specific potassium leak channel Kcnk9 for maternal expression prior to neurogenesis. In contrast, this enhancer-promoter contact is blocked by CTCF on the paternal allele, preventing paternal Kcnk9 activation. This work provides a high-resolution map of imprinted chromatin structure and demonstrates that chromatin state established in early development can promote imprinted expression upon differentiation.
|
| |
|
| Overall design |
Region capture Hi-C of the Peg13-Kcnk9 imprinted locus in mESCs, induced neurons (iNs), and mouse brain, in biological duplicate.
|
| |
|
| Contributor(s) |
Loftus D, Bae B, Whilden CM, Whipple AJ |
| Citation(s) |
37333073 |
| BioProject |
PRJNA834094 |
| |
| Submission date |
May 04, 2022 |
| Last update date |
Aug 08, 2023 |
| Contact name |
Daniel Loftus |
| E-mail(s) |
danielloftus@g.harvard.edu
|
| Phone |
8307036005
|
| Organization name |
Harvard University
|
| Department |
MCB
|
| Lab |
Whipple Lab
|
| Street address |
16 Divinity Ave, Rm 4004
|
| City |
Cambridge |
| State/province |
Massachusetts |
| ZIP/Postal code |
02138 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
|
| Samples (8)
|
| GSM6107188 |
Region capture Hi-C, iN, rep2 |
| GSM7475314 |
Region capture Hi-C, B6xCAST, rep1 |
| GSM7475315 |
Region capture Hi-C, B6xCAST, rep2 |
| GSM7475316 |
Region capture Hi-C, CASTxB6, rep1 |
| GSM7475317 |
Region capture Hi-C, CASTxB6, rep2 |
|
| Supplementary file |
Size |
Download |
File type/resource |
| GSE202251_BC_maternal_all.header.medium.sorted.txt.gz |
139.1 Mb |
(ftp)(http) |
TXT |
| GSE202251_BC_paternal_all.header.medium.sorted.txt.gz |
128.4 Mb |
(ftp)(http) |
TXT |
| GSE202251_RAW.tar |
235.7 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
|
|
|
|
 |
Less...
More...