Enhancer malfunction in cancer

Hans Martin Herz, Deqing Hu, Ali Shilatifard*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

100 Scopus citations

Abstract

Why certain point mutations in a general transcription factor are associated with specific forms of cancer has been a major question in cancer biology. Enhancers are DNA regulatory elements that are key regulators of tissue-specific gene expression. Recent studies suggest that enhancer malfunction through point mutations in either regulatory elements or factors modulating enhancer-promoter communication could be the cause of tissue-specific cancer development. In this Perspective, we will discuss recent findings in the identification of cancer-related enhancer mutations and the role of Drosophila Trr and its human homologs, the MLL3 and MLL4/COMPASS-like complexes, as enhancer histone H3 lysine 4 (H3K4) monomethyltransferases functioning in enhancer-promoter communication. Recent genome-wide studies in the cataloging of somatic mutations in cancer have identified mutations in intergenic sequences encoding regulatory elements-and in MLL3 and MLL4 in both hematological malignancies and solid tumors. We propose that cancer-associated mutations in MLL3 and MLL4 exert their properties through the malfunction of Trr/MLL3/MLL4-dependent enhancers.

Original languageEnglish (US)
Pages (from-to)859-866
Number of pages8
JournalMolecular cell
Volume53
Issue number6
DOIs
StatePublished - Mar 20 2014

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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