dorsal/arxiv
View SchemaThe promoters of human cell cycle genes integrate signals from two tumor suppressive pathways during cellular transformation
| Authors | Yuval Tabach, Michael Milyavsky, Igor Shats, Ran Brosh, Or Zuk, Assif Yitzhaky, Roberto Mantovani, Eytan Domany, Varda Rotter Yitzhak Pilpel |
|---|---|
| Categories | |
| ArXiv ID | q-bio/0511022 |
| URL | https://arxiv.org/abs/q-bio/0511022 |
Abstract
Deciphering regulatory events that drive malignant transformation represents a major challenge for systems biology. Here we analyzed genome-wide transcription profiling of an in-vitro transformation process. We focused on a cluster of genes whose expression levels increased as a function of p53 and p16INK4A tumor suppressors inactivation. This cluster predominantly consists of cell cycle genes and constitutes a signature of a diversity of cancers. By linking expression profiles of the genes in the cluster with the dynamic behavior of p53 and p16INK4A, we identified a promoter architecture that integrates signals from the two tumor suppressive channels and that maps their activity onto distinct levels of expression of the cell cycle genes, which in turn, correspond to different cellular proliferation rates. Taking components of the mitotic spindle as an example, we experimentally verified our predictions that p53-mediated transcriptional repression of several of these novel targets is dependent on the activities of p21, NFY and E2F. Our study demonstrates how a well-controlled transformation process allows linking between gene expression, promoter architecture and activity of upstream signaling molecules.
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"abstract": "Deciphering regulatory events that drive malignant transformation represents\na major challenge for systems biology. Here we analyzed genome-wide\ntranscription profiling of an in-vitro transformation process. We focused on a\ncluster of genes whose expression levels increased as a function of p53 and\np16INK4A tumor suppressors inactivation. This cluster predominantly consists of\ncell cycle genes and constitutes a signature of a diversity of cancers. By\nlinking expression profiles of the genes in the cluster with the dynamic\nbehavior of p53 and p16INK4A, we identified a promoter architecture that\nintegrates signals from the two tumor suppressive channels and that maps their\nactivity onto distinct levels of expression of the cell cycle genes, which in\nturn, correspond to different cellular proliferation rates. Taking components\nof the mitotic spindle as an example, we experimentally verified our\npredictions that p53-mediated transcriptional repression of several of these\nnovel targets is dependent on the activities of p21, NFY and E2F. Our study\ndemonstrates how a well-controlled transformation process allows linking\nbetween gene expression, promoter architecture and activity of upstream\nsignaling molecules.",
"arxiv_id": "q-bio/0511022",
"authors": [
"Yuval Tabach",
"Michael Milyavsky",
"Igor Shats",
"Ran Brosh",
"Or Zuk",
"Assif Yitzhaky",
"Roberto Mantovani",
"Eytan Domany",
"Varda Rotter Yitzhak Pilpel"
],
"categories": [
"q-bio.MN",
"q-bio.QM"
],
"title": "The promoters of human cell cycle genes integrate signals from two tumor suppressive pathways during cellular transformation",
"url": "https://arxiv.org/abs/q-bio/0511022"
},
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