Abstract
Various types of data, including genomic sequences, transcription factor (TF) knockout data, TF-DNA interaction and expression profiles, have been used to decipher TF regulatory mechanisms. However, most of the genes affected by knockout of a particular TF are not bound by that factor. Here, I showed that this interesting result can be partially explained by considering the nuclear positioning of TF knockout affected genes and TF bound genes. I found that a statistically significant number of TF knockout affected genes show nuclear colocalization with genes bound by the corresponding TF. Although these TF knockout affected genes are not directly bound by the corresponding TF; the TF tend to be in the same cellular component with the TFs that directly bind these genes. TF knockout affected genes show co-expression and tend to be involved in the same biological process with the spatially adjacent genes that are bound by the corresponding TF. These results demonstrate that TFs can regulate genes through nuclear colocalization without direct DNA binding, complementing the conventional view that TFs directly bind DNA to regulate genes. My findings will have implications in understanding TF regulatory mechanisms.
Highlights
Transcription factor (TF) binds DNA recognition sites in genomic regulatory regions to control genomic transcription
Chromatin immunoprecipitation followed by microarray hybridization (ChIP-chip) is a wonderful tool for studying direct physical information of binding between TF and DNA regions [1,2,3]
TF-KO Genes Show Nuclear Colocalization with Genes Bound by the Corresponding TF
Summary
Transcription factor (TF) binds DNA recognition sites in genomic regulatory regions to control genomic transcription. There are two main methods to determine genome-wide TF direct targets. Chromatin immunoprecipitation followed by microarray hybridization (ChIP-chip) is a wonderful tool for studying direct physical information of binding between TF and DNA regions [1,2,3]. Mammals, chromatin immunoprecipitation coupled with massively parallel sequencing (ChIP-seq) is a widely used method for mapping direct physical TF-DNA interactions genome-wide [4,5]. ChIP-chip and ChIP-seq assays are effective in uncovering genome-wide maps of the locations bound by the immunoprecipitated
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