Open chromatin and ATAC-seq

Nathan Sheffield, PhD

What does the genome encode?

Regulatory DNA is important

Challenges to studying regulatory DNA

  • Variation: age, cell-type, environment, disease
  • Amount: 2% protein coding vs 25%? regulatory
  • Target: what gene does it affect?
  • Function: is it a promoter, silencer, insulator, enhancer?
  • Rigidity: genetic code vs TF motifs

We can computationally identify genes and even predict function. Regulatory DNA is more difficult.

How can we identify regulatory DNA?

Alberts 2002

How can we identify regulatory DNA?

  • DNase: classic 'gold standard' to identify open chromatin
  • FAIRE: Formaldehyde-assisted isolation of regulatory elements
  • ChIP: Chromatin immunoprecipitation
  • ATAC: Assay for transposase-accessible chromatin

DNase-seq: Biology


ATAC-seq: Experiment (Buenrostro et al. 2013)

Chromatin and transcription factors (Thurman et al. 2012)

Chromatin accessibility across cell types

Vernon et al. 2012


  • Open chromatin coincides with active regulatory DNA
  • ... but exact annotation or binding is not provided
  • ChIP seq advantage and disadvantage is in its target. it also requires antibodies and provides more diffuse signal

How can we identify what regulatory DNA is doing?

Image credit: "The genetic code" by OpenStax College, Biology.