Abstract
Aberrant accumulation of the Myc oncoprotein propels proliferation and induces carcinogenesis. In normal cells, however, an abundance of Myc protein represses transcription at the c-myc locus. Cancer cells often lose this autorepression. We examined the control of myc in Drosophila and show here that the Drosophila ortholog, dmyc, also undergoes autorepression. We find that the developmental repressor Polycomb (Pc) is required for dmyc autorepression, and that this Pc-dMyc-mediated repression spreads across an 875-kb region encompassing the dmyc gene. To further investigate the relationship between Myc and Polycomb, we used microarrays to identify genes regulated by each, and identify a striking relationship between the two: A large set of dMyc activation targets is normally repressed by Pc, and 73% of dMyc repression targets require Pc for this repression. Chromatin immunoprecipitation confirmed that many dMyc-Pc-repressed loci have an epigenetic mark recognized by Pc. Our results suggest a novel relationship between Myc and Polycomb, wherein Myc enhances Polycomb repression in order to repress targets, and Myc suppresses Polycomb repression in order to activate targets.
References
26
Referenced
36
10.1126/science.1076997
10.1146/annurev.ge.20.120186.002045
10.1016/S0092-8674(02)00975-3
10.1101/gad.1110503
10.1126/science.1100576
10.1126/science.274.5292.1523
10.1016/S0092-8674(00)80944-7
10.1002/j.1460-2075.1990.tb07612.x
/ EMBO J. (1990)10.1038/16476
10.1016/S0092-8674(00)81512-3
10.1016/S0092-8674(00)81725-0
10.1002/dvg.1020150505
10.1016/S0091-679X(08)60933-4
10.1038/276565a0
10.1242/dev.00932
10.1101/gad.269603
10.1016/S0092-8674(02)00976-5
10.1016/S0065-230X(02)84004-0
10.1002/j.1460-2075.1990.tb08217.x
/ EMBO J. (1990)10.1242/dev.01108
10.1016/j.molcel.2004.10.015
10.1038/383627a0
10.1073/pnas.94.4.1235
10.1038/414768a
10.1016/0092-8674(91)90382-9
10.1101/gad.12.24.3803
Dates
Type | When |
---|---|
Created | 19 years, 8 months ago (Dec. 15, 2005, 3:52 p.m.) |
Deposited | 3 years, 9 months ago (Nov. 16, 2021, 11:43 a.m.) |
Indexed | 1 year, 2 months ago (June 12, 2024, 10:22 p.m.) |
Issued | 19 years, 8 months ago (Dec. 15, 2005) |
Published | 19 years, 8 months ago (Dec. 15, 2005) |
Published Online | 19 years, 8 months ago (Dec. 15, 2005) |
Published Print | 19 years, 8 months ago (Dec. 15, 2005) |
@article{Goodliffe_2005, title={Polycomb mediates Myc autorepression and its transcriptional control of many loci in Drosophila}, volume={19}, ISSN={1549-5477}, url={http://dx.doi.org/10.1101/gad.1352305}, DOI={10.1101/gad.1352305}, number={24}, journal={Genes & Development}, publisher={Cold Spring Harbor Laboratory}, author={Goodliffe, Julie M. and Wieschaus, Eric and Cole, Michael D.}, year={2005}, month=dec, pages={2941–2946} }