Developmental stage specific chromosome architecture in human erythroid cells
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA396999 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR5890790_1.fastq.gz | Fastqsanger.gz | |||
| SRR5890790_2.fastq.gz | Fastqsanger.gz | |||
| SRR5890800_1.fastq.gz | Fastqsanger.gz | |||
| SRR5890800_2.fastq.gz | Fastqsanger.gz | |||
| SRR5890810_1.fastq.gz | Fastqsanger.gz |
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Project description:Chromatin structure is tightly intertwined with transcription regulation. Here we compared the chromosomal architectures of fetal and adult human erythroblasts and find that globally, chromatin structures and compartments A/B are highly similar at both developmental stages. At a finer scale, we detect distinct folding patterns at the developmentally controlled b-globin locus. Specifically, new fetal stage-specific contacts are uncovered between a region separating the fetal (g-) and adult (b-) globin genes (encompassing the HBBP1 and BGLT3 non-coding genes) and two distal chromosomal sites (HS5 and 3'HS1) that flank the locus. In contrast, in adult cells the HBBP1-BGLT3 region contacts the embryonic e-globin gene, physically separating the fetal globin genes from the enhancer (LCR). Removal of the HBBP1 gene strongly reactivates g-globin expression, accompanied by increased LCR-g-globin and decreased BGLT3-e-globin interactions, mimicking the effects of deleting the fetal globin repressor BCL11A. Our results uncover a new critical regulatory region as a potential target for therapeutic genome editing for hemoglobinopathies and highlight the power of chromosome conformation analysis in discovering new cis control elements.
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