The most common mutation in human melanoma, BRAF(V600E), activates the serine/threonine kinase BRAF and causes excessive activity in the mitogen-activated protein kinase pathway. BRAF(V600E) mutations are also present in benign melanocytic naevi, highlighting the importance of additional genetic alterations in the genesis of malignant tumours. Such changes include recurrent copy number variations that result in the amplification of oncogenes. For certain amplifications, the large number of genes in the interval has precluded an understanding of the cooperating oncogenic events. Here we have used a zebrafish melanoma model to test genes in a recurrently amplified region of chromosome 1 for the ability to cooperate with BRAF(V600E) and accelerate melanoma. SETDB1, an enzyme that methylates histone H3 on lysine 9 (H3K9), was found to accelerate melanoma formation significantly in zebrafish. Chromatin immunoprecipitation coupled with massively parallel DNA sequencing and gene expression analyses uncovered genes, including HOX genes, that are transcriptionally dysregulated in response to increased levels of SETDB1. Our studies establish SETDB1 as an oncogene in melanoma and underscore the role of chromatin factors in regulating tumo...Continue Reading
Immunohistochemical study of the proliferation index, oestrogen receptors and progesterone receptors A and B in leiomyomata and normal myometrium during the menstrual cycle and under gonadotrophin-releasing hormone agonist therapy
PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes
mAM facilitates conversion by ESET of dimethyl to trimethyl lysine 9 of histone H3 to cause transcriptional repression
Methyl-CpG binding protein MBD1 couples histone H3 methylation at lysine 9 by SETDB1 to DNA replication and chromatin assembly
BRAF mutations are sufficient to promote nevi formation and cooperate with p53 in the genesis of melanoma
Integrative genomic analyses identify MITF as a lineage survival oncogene amplified in malignant melanoma
Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles
Assessing the significance of chromosomal aberrations in cancer: methodology and application to glioma.
Expression of H-RASV12 in a zebrafish model of Costello syndrome causes cellular senescence in adult proliferating cells.
SetDB1 contributes to repression of genes encoding developmental regulators and maintenance of ES cell state.
A subset of the histone H3 lysine 9 methyltransferases Suv39h1, G9a, GLP, and SETDB1 participate in a multimeric complex
Molecular characterization of zebrafish embryogenesis via DNA microarrays and multiplatform time course metabolomics studies
SPOC1 modulates DNA repair by regulating key determinants of chromatin compaction and DNA damage response.
Abrogation of BRAFV600E-induced senescence by PI3K pathway activation contributes to melanomagenesis.
Intratumoral genetic heterogeneity in metastatic melanoma is accompanied by variation in malignant behaviors
An ENU mutagenesis screen identifies novel and known genes involved in epigenetic processes in the mouse
Studying synthetic lethal interactions in the zebrafish system: insight into disease genes and mechanisms.
H. pylori virulence factor CagA increases intestinal cell proliferation by Wnt pathway activation in a transgenic zebrafish model
Integrated genomic and gene expression profiling identifies two major genomic circuits in urothelial carcinoma.
Deep mRNA sequencing analysis to capture the transcriptome landscape of zebrafish embryos and larvae
Detailed Analysis of Focal Chromosome Arm 1q and 6p Amplifications in Urothelial Carcinoma Reveals Complex Genomic Events on 1q, and SOX4 as a Possible Auxiliary Target on 6p
Gene expression analysis of zebrafish melanocytes, iridophores, and retinal pigmented epithelium reveals indicators of biological function and developmental origin
The transcriptional cofactor MCAF1/ATF7IP is involved in histone gene expression and cellular senescence
Liver tumor models in transgenic zebrafish: an alternative in vivo approach to study hepatocarcinogenes
A meta-analysis of multiple matched copy number and transcriptomics data sets for inferring gene regulatory relationships
Role of histone lysine methyltransferases SUV39H1 and SETDB1 in gliomagenesis: modulation of cell proliferation, migration, and colony formation
Immunohistochemistry for histone h3 lysine 9 methyltransferase and demethylase proteins in human melanomas
Histone 3 lysine 9 trimethylation is differentially associated with isocitrate dehydrogenase mutations in oligodendrogliomas and high-grade astrocytomas
Cancer Epigenetics Chromatin Complexes (Keystone)
Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. This feed focuses on chromatin complexes and their role in cancer epigenetics.
Cancer Epigenetics and Chromatin (Keystone)
Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. This feed focuses on chromatin and its role in cancer epigenetics please follow this feed to learn more.