Abstract PR06: Analysis of enhancer transcription reveals novel gene regulatory networks in breast cancer

Enhancer transcription is a defining feature of active enhancers. We and others have shown that enhancers that produce transcripts (so called “eRNAs”) are more likely to (1) be associated with active chromatin marks, such as H3K4me1 and K3K27ac, (2) loop to target gene promoters, and (3) be associated with target gene activation. Thus, enhancer transcription is a good predictor of active enhancers. In this regard, we have shown that enhancer transcription can be used in the absence of any other genomic information to predict enhancers. We have used Global Run-On coupled deep sequencing (GRO-seq) in 14 different breast cancer cell lines representing the five distinct molecular subtypes of breast cancer, coupled with a computational pipeline that we have developed, to predict enhancers based solely on enhancer transcription. We found both common and unique sites of enhancer transcription across the cell lines. In addition, we observed that enhancer transcription correlates with nearest gene transcription. Unsupervised hierarchical clustering of enhancer transcription was sufficient to segregate the breast cancer cell lines into their specific molecular subtypes. Transcription factor motif analysis performed at the sites of enhancer transcription identified transcription factors that may be important for the transcriptional programs of each cell type. Transcription factors whose motifs were uniquely enriched in a specific cell type were observed to be bound at the enhancers ...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Enhancers Source Type: research