Genomics

Dataset Information

296

Essential role of microphthalmia transcription factor for DNA replication, mitosis and genomic stability in melanoma


ABSTRACT: Malignant melanoma is an aggressive cancer known for its notorious resistance to most current therapies. The basic helix-loop-helix microphthalmia transcription factor (MITF) is the master regulator determining the identity and properties of the melanocyte lineage, and is regarded as a lineage-specific ‘oncogene’ that has a critical role in the pathogenesis of melanoma. MITF promotes melanoma cell proliferation, whereas sustained supression of MITF expression leads to senescence. By combining chromatin immunoprecipitation coupled to high throughput sequencing (ChIP-seq) and RNA sequen- cing analyses, we show that MITF directly regulates a set of genes required for DNA replication, repair and mitosis. Our results reveal how loss of MITF regulates mitotic fidelity, and through defective replication and repair induces DNA damage, ultimately ending in cellular senescence. These findings reveal a lineage-specific control of DNA replication and mitosis by MITF, providing new avenues for therapeutic intervention in melanoma. The identification of MITF-binding sites and gene- regulatory networks establish a framework for under- standing oncogenic basic helix-loop-helix factors such as N-myc or TFE3 in other cancers. 4 samples corresponding to genomic occupancy profiling of MITF (Cl8), PolII (501Mel), H3K4me3 501Mel). Anti-HA ChIP-seq on untagged cell line (501Mel) was used as a control.

ORGANISM(S): Homo sapiens  

SUBMITTER: Patrick Laurette   Stephanie LeGras  Thomas Strub  Irwin Davidson 

PROVIDER: E-GEOD-64137 | ArrayExpress | 2014-12-13

SECONDARY ACCESSION(S): GSE64137SRP051112PRJNA270236

REPOSITORIES: GEO, ArrayExpress, ENA

altmetric image

Publications

Essential role of microphthalmia transcription factor for DNA replication, mitosis and genomic stability in melanoma.

Strub T T   Giuliano S S   Ye T T   Bonet C C   Keime C C   Kobi D D   Le Gras S S   Cormont M M   Ballotti R R   Bertolotto C C   Davidson I I  

Oncogene 20110124 20


Malignant melanoma is an aggressive cancer known for its notorious resistance to most current therapies. The basic helix-loop-helix microphthalmia transcription factor (MITF) is the master regulator determining the identity and properties of the melanocyte lineage, and is regarded as a lineage-specific 'oncogene' that has a critical role in the pathogenesis of melanoma. MITF promotes melanoma cell proliferation, whereas sustained supression of MITF expression leads to senescence. By combining ch  ...[more]

Similar Datasets

2015-04-02 | E-GEOD-61966 | ArrayExpress
2015-09-07 | E-GEOD-61966 | ExpressionAtlas
2010-01-01 | E-GEOD-16249 | ArrayExpress
2014-01-14 | E-GEOD-50681 | ArrayExpress
2014-01-14 | E-GEOD-50649 | ArrayExpress
2016-01-13 | PXD002565 | Pride
2010-01-02 | GSE16249 | GEO
2015-10-29 | E-GEOD-71798 | ArrayExpress
2014-12-24 | E-GEOD-64497 | ArrayExpress
2015-07-30 | E-GEOD-69403 | ArrayExpress