Format

Send to

Choose Destination
Mol Cell. 2014 Oct 23;56(2):275-285. doi: 10.1016/j.molcel.2014.08.016. Epub 2014 Sep 18.

DNase footprint signatures are dictated by factor dynamics and DNA sequence.

Author information

1
Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, NIH, Building 41, 41 Library Drive, Bethesda, MD 20892, USA.
2
Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, NIH, Building 41, 41 Library Drive, Bethesda, MD 20892, USA. Electronic address: hagerg@exchange.nih.gov.

Abstract

Genomic footprinting has emerged as an unbiased discovery method for transcription factor (TF) occupancy at cognate DNA in vivo. A basic premise of footprinting is that sequence-specific TF-DNA interactions are associated with localized resistance to nucleases, leaving observable signatures of cleavage within accessible chromatin. This phenomenon is interpreted to imply protection of the critical nucleotides by the stably bound protein factor. However, this model conflicts with previous reports of many TFs exchanging with specific binding sites in living cells on a timescale of seconds. We show that TFs with short DNA residence times have no footprints at bound motif elements. Moreover, the nuclease cleavage profile within a footprint originates from the DNA sequence in the factor-binding site, rather than from the protein occupying specific nucleotides. These findings suggest a revised understanding of TF footprinting and reveal limitations in comprehensive reconstruction of the TF regulatory network using this approach.

Comment in

PMID:
25242143
PMCID:
PMC4272573
DOI:
10.1016/j.molcel.2014.08.016
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center