Multiple roles for the mll/compass family in the epigenetic regulation of gene expression and in cancer

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

The mixed lineage leukemia (MLL) gene is involved in numerous chromosomal translocations that result in acute myeloid and acute lymphoid leukemias. The MLL protein belongs to a family of six methyltransferases in mammals that can methylate histone H3 on lysine 4 (H3K4). The methyltransferase activities of MLL and the other family members, SETD1A, SETD1B, MLL2, MLL3 and MLL4, depend on their participation within macromolecular complexes called COMPASS (complex of proteins associated with Set1). Functional diversity within the COMPASS family includes the propensity to mono-, di-, or trimethylate H3K4 and to regulate promoters or enhancers. Recent cancer genome sequencing and animal studies have identified MLL3 and MLL4 as cancer drivers in a wide variety of hematologic and solid tumors. MLL3 and MLL4 implement monomethylation of H3K4 at enhancer regions, whereas another enzyme in MLL3 and MLL4 COMPASS, UTX, which is also frequently mutated in multiple types of cancer, demethylates H3K27me3, a modification associated with transcription repression by the Polycomb group of proteins. Here, we review the different roles for the COMPASS family in cancer and suggest directions for future research toward elucidating the cellular pathways disregulated due to altered COMPASS functions.

Original languageEnglish (US)
Pages (from-to)425-446
Number of pages22
JournalAnnual Review of Cancer Biology
Volume1
DOIs
StatePublished - 2017

Keywords

  • Enhancer
  • Histone modification
  • Mixed-lineage leukemia
  • Transcription elongation
  • Tumor suppressor

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Oncology

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