Format

Send to

Choose Destination
Mol Cell. 2014 Mar 20;53(6):859-66. doi: 10.1016/j.molcel.2014.02.033.

Enhancer malfunction in cancer.

Author information

1
Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
2
Stowers Institute for Medical Research, Kansas City, MO 64110, USA. Electronic address: ash@stowers.org.

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.

PMID:
24656127
PMCID:
PMC4049186
DOI:
10.1016/j.molcel.2014.02.033
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center