BINOCh
Binding Inference from Nucleosome Occupancy Changes

Summary

Transcription factor binding events often leave a trace pattern of nucleosome occupancy changes in which nucleosomes flanking the binding site increase in occupancy while those in the vicinity of the binding site itself are displaced. Genome wide information on enhancer proximal nucleosome occupancy can be readily acquired using ChIP-seq targeting enhancer related histone modifications such as H3K4me2. Here we present a software package, BINOCh, that allows biologists to use such data to infer the identity of key transcription factors that regulate the response of a cell to a stimulus or determine a program of differentiation.

Introduction

Transcription factors regulate gene expression by binding to the genome in a cell-type and condition dependent manner. Although transcription factors are known to have a high affinity to specific DNA sequences, DNA sequence alone is a poor predictor of in vivo genome wide transcription factor binding locations. When the relevant transcription factors are known and suitable antibodies are available, ChIP-chip and ChIP-seq technologies enable us to map their genome-wide binding locations, one factor, sample type and condition at a time. In many cases, however, the transcription factors governing a regulatory response are not known or antibodies suitable for ChIP-seq are not available. Without transcription factor specific antibodies it is nevertheless possible to infer transcription factor binding events based on two recent observations. First, transcription factor binding sites are often associated with certain types of post-translational histone modifications, in particular histone H3 lysine 4 mono- and di-methylation. Second, transcription factor binding is frequently associated with a pattern of nucleosome occupancy changes in which nucleosomes flanking the binding site increase in occupancy while those in the vicinity of the binding site itself are displaced. Transcription factor binding events can therefore be infered by comparing nucleosome resolution H3K4me1/2 ChIP-seq data under treatment and control conditions.

Author

Cliff Meyer.

Contact

If you have any comments, suggestions, questions, bug reports, etc, feel free to contact Cliff Meyer ( cliff at jimmy dot harvard dot edu ). And PLEASE attach your command line and log messages if possible.

If you think your question/comment may be interesting to the BINOCh user group, please post it to our google group.