EXPERIMENT_TITLE: Hi-C
STUDY_DESCRIPTOR_STUDY_ABSTRACT: Prader-Willi Syndrome (PWS) is caused by loss of expression of paternally expressed genes in the human 15q11.2-q13 imprinting domain. A set of imprinted genes that are active on the paternal but silenced on the maternal chromosome are intricately regulated by a bipartite imprinting center (PWS-IC) located in the PWS imprinting domain. In past work, we discovered that euchromatic histone lysine N-methyltransferase-2 (EHMT2/G9a) inhibitors were capable of un-silencing PWS-associated genes by restoring their expression from the maternal chromosome. Here, in mice lacking the Ehmt2 gene, we document un-silencing of the imprinted Snrpn/Snhg14 gene on the maternal chromosome in the late embryonic and postnatal brain. Using PWS and Angelman syndrome patient derived cells with either paternal or maternal deletion of 15q11-q13, we have found that chromatin of maternal PWS-IC is closed and has compact 3D folding confirmation. We further show that a new and distinct noncoding RNA preferentially transcribed from upstream of the PWS-IC interacts with EHMT2 and forms a heterochromatin complex to silence gene expression of SNRPN in CIS on maternal chromosome. Taken together, these findings demonstrate that allele-specific recruitment of EHMT2 is required to maintain the maternal imprints. Our findings provide novel mechanistic insights and support a new model for imprinting maintenance of the PWS imprinted domain.
SAMPLE_TITLE: Hi-C
SAMPLE_SAMPLE_ATTRIBUTES_SAMPLE_ATTRIBUTE: [{"TAG": "isolate", "VALUE": "skin"}, {"TAG": "age", "VALUE": "unknown"}, {"TAG": "biomaterial_provider", "VALUE": "Baylor university"}, {"TAG": "collection_date", "VALUE": "2022-09-04"}, {"TAG": "geo_loc_name", "VALUE": "USA"}, {"TAG": "sex", "VALUE": "male"}, {"TAG": "tissue", "VALUE": "skin fibroblasts"}, {"TAG": "disease", "VALUE": "Prader-willi syndrome"}, {"TAG": "replicates", "VALUE": "1"}, {"TAG": "BioSampleModel", "VALUE": "Human"}]
Pool_Member_@attributes_sample_title: Hi-C
RUN_SET_RUN_Pool_Member_@attributes_sample_title: Hi-C
RUN_SET_RUN_SRAFiles_SRAFile: [{"Alternatives": null, "@attributes": {"cluster": "public", "filename": "PWS-FB-HiC_325_252_S28_L001_R1_001.fastq", "size": "65317", "date": "2024-11-19 11:43:11", "md5": "38c286bdb161b3ddc3b070538585524f", "version": "1", "semantic_name": "fastq", "supertype": "Original", "sratoolkit": "0"}}, {"Alternatives": null, "@attributes": {"cluster": "public", "filename": "PWS-FB-HiC_325_252_S28_L001_R2_001.fastq", "size": "65317", "date": "2024-11-19 11:43:13", "md5": "48aa70378b8621917fbf91f6e16bf666", "version": "1", "semantic_name": "fastq", "supertype": "Original", "sratoolkit": "0"}}, {"Alternatives": [null, null, null], "@attributes": {"cluster": "public", "filename": "SRR31397360", "url": "https://sra-downloadb.be-md.ncbi.nlm.nih.gov/sos7/sra-pub-run-38/SRR031/31397/SRR31397360/SRR31397360.1", "size": "82881", "date": "2024-11-19 11:43:30", "md5": "f5b707b3f20157c6ee83da074f0d4946", "version": "1", "semantic_name": "SRA Normalized", "supertype": "Primary ETL", "sratoolkit": "1"}}]