An Intergenic Regulatory Region Mediates Drosophila Myc -Induced Apoptosis and Blocks Tissue Hyperplasia

Moreno, Eduardo; Zhang, C; Casas-Tintó, S; Li, G; Lin, N; Chung, M; Moberg, K H; Zhou, L (2015). An Intergenic Regulatory Region Mediates Drosophila Myc -Induced Apoptosis and Blocks Tissue Hyperplasia. Oncogene, 34(18), pp. 2385-2397. Nature Publishing Group 10.1038/onc.2014.160

[img] Text
ZhouMobergMoreno.pdf - Published Version
Restricted to registered users only
Available under License Publisher holds Copyright.

Download (6MB) | Request a copy

Induction of cell-autonomous apoptosis following oncogene-induced overproliferation is a major tumor-suppressive mechanism in vertebrates. However, the detailed mechanism mediating this process remains enigmatic. In this study, we demonstrate that dMyc-induced cell-autonomous apoptosis in the fruit fly Drosophila melanogaster relies on an intergenic sequence termed the IRER (irradiation-responsive enhancer region). The IRER mediates the expression of surrounding proapoptotic genes, and we use an in vivo reporter of the IRER chromatin state to gather evidence that epigenetic control of DNA accessibility within the IRER is an important determinant of the strength of this response to excess dMyc. In a previous work, we showed that the IRER also mediates P53-dependent induction of proapoptotic genes following DNA damage, and the chromatin conformation within IRER is regulated by polycomb group-mediated histone modifications. dMyc-induced apoptosis and the P53-mediated DNA damage response thus overlap in a requirement for the IRER. The epigenetic mechanisms controlling IRER accessibility appear to set thresholds for the P53- and dMyc-induced expression of apoptotic genes in vivo and may have a profound impact on cellular sensitivity to oncogene-induced stress.

Item Type:

Journal Article (Original Article)

Division/Institute:

08 Faculty of Science > Department of Biology > Institute of Cell Biology

UniBE Contributor:

Moreno, Eduardo

Subjects:

500 Science > 570 Life sciences; biology

ISSN:

0950-9232

Publisher:

Nature Publishing Group

Language:

English

Submitter:

Eduardo Moreno

Date Deposited:

01 Jun 2016 14:45

Last Modified:

01 Jun 2016 14:45

Publisher DOI:

10.1038/onc.2014.160

PubMed ID:

24931167

BORIS DOI:

10.7892/boris.82419

URI:

https://boris.unibe.ch/id/eprint/82419

Actions (login required)

Edit item Edit item
Provide Feedback