Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA924005 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Other | ||||
| SRR23117880_1.fastq.gz | Fastqsanger.gz | |||
| SRR23448854_1.fastq.gz | Fastqsanger.gz | |||
| SRR23448855_1.fastq.gz | Fastqsanger.gz | |||
| SRR23448856_1.fastq.gz | Fastqsanger.gz |
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Project description:The cohesin complex is central to chromatin looping, but mechanisms by which these long-range chromatin interactions are formed and persist remain unclear. We demonstrate that interactions between a transcription factor and the cohesin loader NIPBL regulate enhancer-promoter looping and promote long-range gene regulation. Using mass-spectrometry, genome mapping, and single-molecule tracking methods, we demonstrate that NIPBL and cohesin regulate the dynamics and function of the glucocorticoid receptor (GR). Moreover, glucocorticoid treatment stabilizes NIPBL and cohesin interactions by promoting loop extrusion and chromatin looping. Patient-derived acute myeloid leukemia cells harboring cohesin mutations exhibit a reduced response to glucocorticoids (GCs), suggesting that the GR-NIPBL-cohesin interaction is defective in these patients, and they may be poor candidates for GC treatment.
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Project description:We present a long-read, single-molecule mapping technology that generates hybrid genetic/epigenetic profiles of native chromosomal DNA. The genome-wide distribution of 5-hmC in human peripheral blood cells correlates well with 5-hmC DNA immunoprecipitation (hMeDIP) sequencing. However, the long single-molecule read-length of 100 kbp-1 Mbp produces 5-hmC profiles across variable genomic regions that failed to show up in the sequencing data. In addition, optical 5-hmC mapping shows a strong correlation between the 5-hmC density in gene bodies and the corresponding level of gene expression.
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