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Computational construction of 3D chromatin ensembles and prediction of functional interactions of alpha-globin locus from 5C data
- Source :
- Nucleic Acids Research
- Publication Year :
- 2017
- Publisher :
- Oxford University Press (OUP), 2017.
-
Abstract
- Conformation capture technologies measure frequencies of interactions between chromatin regions. However, understanding gene-regulation require knowledge of detailed spatial structures of heterogeneous chromatin in cells. Here we describe the nC-SAC (n-Constrained-Self Avoiding Chromatin) method that transforms experimental interaction frequencies into 3D ensembles of chromatin chains. nC-SAC first distinguishes specific from non-specific interaction frequencies, then generates 3D chromatin ensembles using identified specific interactions as spatial constraints. Application to α-globin locus shows that these constraints (∼20%) drive the formation of ∼99% all experimentally captured interactions, in which ∼30% additional to the imposed constraints is found to be specific. Many novel specific spatial contacts not captured by experiments are also predicted. A subset, of which independent ChIA-PET data are available, is validated to be RNAPII-, CTCF-, and RAD21-mediated. Their positioning in the architectural context of imposed specific interactions from nC-SAC is highly important. Our results also suggest the presence of a many-body structural unit involving α-globin gene, its enhancers, and POL3RK gene for regulating the expression of α-globin in silent cells.
- Subjects :
- 0301 basic medicine
CCCTC-Binding Factor
Protein Conformation
Cell Cycle Proteins
Locus (genetics)
DNA-Directed DNA Polymerase
Computational biology
Regulatory Sequences, Nucleic Acid
Biology
DNA-binding protein
03 medical and health sciences
0302 clinical medicine
Protein structure
alpha-Globins
Cell Line, Tumor
Genetics
Humans
Enhancer
Gene
Regulation of gene expression
Computational Biology
Nuclear Proteins
Phosphoproteins
Chromatin
DNA-Binding Proteins
030104 developmental biology
Gene Expression Regulation
CTCF
K562 Cells
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 13624962 and 03051048
- Volume :
- 45
- Database :
- OpenAIRE
- Journal :
- Nucleic Acids Research
- Accession number :
- edsair.doi.dedup.....b0f66209bfce9d56ac748d6e21f7e6c7