A new method to characterize cancer genes

Researchers from the lab of Johannes Zuber at the IMP and the lab of Stefan Ameres at IMBA have deciphered regulatory functions of important cancer genes.

The transcription of active genes into messenger RNAs (mRNAs) is controlled by a complex network of transcriptional regulators. Mutations in these regulators can lead to cancer and other human diseases. At the same time, blocking abnormal transcription can kill cancer cells, making some transcriptional regulators possible targets for drug development.

In the past, it has been difficult to determine which genes these transcriptional regulators control because methods, such as mRNA sequencing, cannot distinguish direct targets of a regulator from indirect effects. Instead of measuring all mRNAs in a cell, SLAMseq – recently developed by the lab of Stefan Ameres – enables the detection of mRNAs that are newly made during a defined period of time.

The researchers used SLAMseq to investigate direct targets of cancer genes and targeted drugs. They thereby characterized the function of two important transcriptional regulators, BRD4 and MYC, which are pursued as possible drug targets in cancer. The results of the successful study have now been published in “Science”.

 

Original Publication:

Muhar, M., et al. (2018): “SLAMseq defines direct gene-regulatory functions of the BRD4-MYC axis.”

Science, 5 April 2018
http://science.sciencemag.org/content/early/2018/04/04/science.aao2793