Abstract
ChIP-seq is used by thousands of research studies to profile histone modifications in cancer. However, methods developed for normal diploid genomes, when applied to cancer samples, can result in false discoveries due to the presence of copy number aberrations distorting the ChIP-seq signal. In order to circumvent this issue, our group has developed a set of ChIP-seq data analysis methods for cancer (http://boevalab.com/tools.html). I will present two of these methods:
• the HMCan method that calls ChIP-seq peaks and normalizes read density profiles for copy number bias [1], and
• the LILY method that identifies super-enhancer regions based on the HMCan output [2].
We applied HMCan and LILY to detect super-enhancer regions in 25 neuroblastoma cell lines and 6 patient derived mouse xenografts. Analysis of super-enhancer landscape in these samples suggested that neuroblastoma cells can be in two different epigenetic and transcriptional states. Single cell analysis showed that both states can co-exist in the same cell line or tumor. The more differentiated state was associated with amplification or high expression of the MYCN oncogene and high activity of noradrenergic transcription factors: PHOX2B, GATA3 and HAND2. The less differentiated state was characterized by the high activity of the AP-1 transcription complex and transcription factors like PRRX1 and RUNX1. Furthermore, we demonstrated that cells in a less differentiated (neural crest-like) state were less sensitive to chemotherapy independently of their genetic background [2].
References:
1. Ashoor et al. Bioinformatics, 2013, 29(23): 2979-2986
2. Boeva et al. Nature Genetics, 2017, 49(9):1408-1413
Meet the speaker
If you want to meet Dr. Valentina Boeva, please book a time slot at https://doodle.com/poll/g5ttsdt7mkh3zira and send an email to anthony.mathelier@ncmm.uio.no.
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Junior talk
Roza Berhanu Lemma, Department of Biosciences, UiO, will present her current research with a talk entitled "The SUMO protease SENP1 and the Chromatin remodeller CHD3 interact, jointly affecting chromatin accessibility and gene expression."