Regulatory Genomics

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

regulatory sequences

By Reddy T. et al (2012) Genome Research. First, for audience not very familiar with the context: Transcription factors: Bind specific DNA motif & controls gene expression Chromatin Immunoprecipitation Sequencing: Cartoon: ChIP-Seq with chips Differential allelic : Alleles are different versions of the same gene. To focus on allelic imbalance means to focus on heterozygotes Differential allelic TF occupancy (DATO): preference to bind one allele over another, within the same cell type Allele specific expression (ASE): Explained in part as functional consequence of differential allelic TF binding EP300: histone acetyltransferase p300, makes DNA more accessible to TF This paper was published in 2012: when exome sequencing was just becoming widely adopted.

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Regulatory elements: Putting enhancers into context

regulatory sequences

Regulatory elements: Putting enhancers into context Principle of suboptimization The enhancer consists of low-affinity TF binding sites in a suboptimal syntax, in terms of flanking nucleotides and spacing between the sites. Optimizing the TF binding affinities can lead to ectopic expression. Experiment In sea squirt, 15 synthetic enhancers consisting of 2 ETS binding sites and a ZicL binding site. Only 2 show activities. Further manipulation confirm key roles for binding site orientation, spacing and flanking nucleotides.

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