TY - JOUR
T1 - Multiple roles for the mll/compass family in the epigenetic regulation of gene expression and in cancer
AU - Meeks, Joshua J.
AU - Shilatifard, Ali
N1 - Funding Information:
We are grateful to Dr. Edwin Smith for helpful discussions, critical reading of this manuscript, and valuable comments. We also want to thank M. Miller for preparation of the figures and L. Shilatifard for editorial assistance. Studies in the Shilatifard laboratory are supported by the National Institutes of Health (R35CA197569).
Publisher Copyright:
© 2017 by Annual Reviews. All rights reserved.
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
KW - Enhancer
KW - Histone modification
KW - Mixed-lineage leukemia
KW - Transcription elongation
KW - Tumor suppressor
UR - http://www.scopus.com/inward/record.url?scp=85057226370&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85057226370&partnerID=8YFLogxK
U2 - 10.1146/annurev-cancerbio-050216-034333
DO - 10.1146/annurev-cancerbio-050216-034333
M3 - Article
AN - SCOPUS:85057226370
SN - 2472-3428
VL - 1
SP - 425
EP - 446
JO - Annual Review of Cancer Biology
JF - Annual Review of Cancer Biology
ER -