Abstract
In vivo protein-DNA interactions connect each transcription factor
with its direct targets to form a gene network scaffold. To map these
protein-DNA interactions comprehensively across entire mammalian
genomes, we developed a large-scale chromatin immunoprecipitation
assay (ChIPSeq) based on direct ultrahigh-throughput DNA sequencing.
This sequence census method was then used to map in vivo binding
of the neuron-restrictive silencer factor (NRSF; also known as REST,
for repressor element-1 silencing transcription factor) to 1946 locations
in the human genome. The data display sharp resolution of binding
position +/-50 base pairs (bp), which facilitated our finding motifs
and allowed us to identify noncanonical NRSF-binding motifs. These
ChIPSeq data also have high sensitivity and specificity ROC (receiver
operator characteristic) area >/= 0.96 and statistical confidence
(P <10(-4)), properties that were important for inferring new candidate
interactions. These include key transcription factors in the gene
network that regulates pancreatic islet cell development.
- algorithms
- amino_acid_motifs
- binding_sites
- chip-seq
- chromatin_immunoprecipitation
- dna,_metabolism
- dna-binding_proteins,_chemistry/metabolism
- gene_regulatory_networks
- genome,_human
- humans
- insulin-secreting_cells,_cytology/physiology
- micrornas,_genetics
- neurons,_physiology
- promoter_regions_(genetics)
- protein_binding
- repressor_proteins,_chemistry/genetics/metabolism
- sensitivity_and_specificity
- sequence_analysis,_dna
- synaptic_transmission
- t-lymphocytes,_metabolism
- transcription,_genetic
- transcription_factors,_chemistry/genetics/metabolism
- zinc_fingers
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