PUBLICATION
Histone 3 Methyltransferases Alter Melanoma Initiation and Progression Through Discrete Mechanisms
- Authors
- DiNapoli, S.E., Martinez-McFaline, R., Shen, H., Doane, A.S., Perez, A.R., Verma, A., Simon, A., Nelson, I., Balgobin, C.A., Bourque, C.T., Yao, J., Raman, R., Béguelin, W., Zippin, J.H., Elemento, O., Melnick, A.M., Houvras, Y.
- ID
- ZDB-PUB-220302-11
- Date
- 2022
- Source
- Frontiers in cell and developmental biology 10: 814216 (Journal)
- Registered Authors
- Bourque, Caitlin, Houvras, Yariv
- Keywords
- epigenetics, histone 3, histone methyl transferase (HMT), melanoma, zebrafish
- Datasets
- GEO:GSE192439, GEO:GSE192436
- MeSH Terms
- none
- PubMed
- 35223844 Full text @ Front Cell Dev Biol
Citation
DiNapoli, S.E., Martinez-McFaline, R., Shen, H., Doane, A.S., Perez, A.R., Verma, A., Simon, A., Nelson, I., Balgobin, C.A., Bourque, C.T., Yao, J., Raman, R., Béguelin, W., Zippin, J.H., Elemento, O., Melnick, A.M., Houvras, Y. (2022) Histone 3 Methyltransferases Alter Melanoma Initiation and Progression Through Discrete Mechanisms. Frontiers in cell and developmental biology. 10:814216.
Abstract
Perturbations to the epigenome are known drivers of tumorigenesis. In melanoma, alterations in histone methyltransferases that catalyze methylation at histone 3 lysine 9 and histone 3 lysine 27-two sites of critical post-translational modification-have been reported. To study the function of these methyltransferases in melanoma, we engineered melanocytes to express histone 3 lysine-to-methionine mutations at lysine 9 and lysine 27, which are known to inhibit the activity of histone methyltransferases, in a zebrafish melanoma model. Using this system, we found that loss of histone 3 lysine 9 methylation dramatically suppressed melanoma formation and that inhibition of histone 3 lysine 9 methyltransferases in human melanoma cells increased innate immune response signatures. In contrast, loss of histone 3 lysine 27 methylation significantly accelerated melanoma formation. We identified FOXD1 as a top target of PRC2 that is silenced in melanocytes and found that aberrant overexpression of FOXD1 accelerated melanoma onset. Collectively, these data demonstrate how histone 3 lysine-to-methionine mutations can be used to uncover critical roles for methyltransferases.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping