Feb 4, 2012

Effects of sequence variation on differential allelic transcription factor occupancy and gene expression

Genome Research
Timothy E ReddyRichard M Myers


A complex interplay between transcription factors (TFs) and the genome regulates transcription. However, connecting variation in genome sequence with variation in TF binding and gene expression is challenging due to environmental differences between individuals and cell types. To address this problem, we measured genome-wide differential allelic occupancy of 24 TFs and EP300 in a human lymphoblastoid cell line GM12878. Overall, 5% of human TF binding sites have an allelic imbalance in occupancy. At many sites, TFs clustered in TF-binding hubs on the same homolog in especially open chromatin. While genetic variation in core TF binding motifs generally resulted in large allelic differences in TF occupancy, most allelic differences in occupancy were subtle and associated with disruption of weak or noncanonical motifs. We also measured genome-wide differential allelic expression of genes with and without heterozygous exonic variants in the same cells. We found that genes with differential allelic expression were overall less expressed both in GM12878 cells and in unrelated human cell lines. Comparing TF occupancy with expression, we found strong association between allelic occupancy and expression within 100 bp of transcription sta...Continue Reading

  • References48
  • Citations64


  • References48
  • Citations64


Mentioned in this Paper

RNA Polymerase II
EP300 protein, human
E1A-Associated p300 Protein
EP300 gene
Sequence Determinations, RNA
Transcription Initiation Site
Chromatin Immunoprecipitation
Plasma Protein Binding Capacity
Gene Expression
Regulatory Elements, Transcriptional

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