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Genes and Development, volume 27, issue 12, pages 1406-1420

Rap1 relocalization contributes to the chromatin-mediated gene expression profile and pace of cell senescence

Platt Jesse M. 1
Ryvkin Paul 2
Wanat Jennifer J. 3
Donahue Greg 4
Ricketts M Dan 5
Barrett Steven P 6
Waters Hannah J 3
Song Shufei 3
Chavez Alejandro 3
Abdallah Khaled Omar 3
Master Stephen R. 3
Wang Li-San 2
Johnson F 3
1
 
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
2
 
2Penn Institute for Biomedical Informatics, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
3
 
1Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
4
 
3Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
5
 
4Wistar Institute, Philadelphia, Pennsylvania 19104, USA
6
 
5Department of Chemistry and Biochemistry, Swarthmore College, Swarthmore, Pennsylvania 19081, USA
Publication typeJournal Article
Publication date2013-06-11
Quartile SCImago
Q1
Quartile WOS
Q1
Impact factor10.5
ISSN08909369, 15495477
Genetics
Developmental Biology
Abstract
Cellular senescence is accompanied by dramatic changes in chromatin structure and gene expression. Using Saccharomyces cerevisiae mutants lacking telomerase (tlc1Δ) to model senescence, we found that with critical telomere shortening, the telomere-binding protein Rap1 (repressor activator protein 1) relocalizes to the upstream promoter regions of hundreds of new target genes. The set of new Rap1 targets at senescence (NRTS) is preferentially activated at senescence, and experimental manipulations of Rap1 levels indicate that it contributes directly to NRTS activation. A notable subset of NRTS includes the core histone-encoding genes; we found that Rap1 contributes to their repression and that histone protein levels decline at senescence. Rap1 and histones also display a target site-specific antagonism that leads to diminished nucleosome occupancy at the promoters of up-regulated NRTS. This antagonism apparently impacts the rate of senescence because underexpression of Rap1 or overexpression of the core histones delays senescence. Rap1 relocalization is not a simple consequence of lost telomere-binding sites, but rather depends on the Mec1 checkpoint kinase. Rap1 relocalization is thus a novel mechanism connecting DNA damage responses (DDRs) at telomeres to global changes in chromatin and gene expression while driving the pace of senescence.

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GOST |
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GOST Copy
Platt J. M. et al. Rap1 relocalization contributes to the chromatin-mediated gene expression profile and pace of cell senescence // Genes and Development. 2013. Vol. 27. No. 12. pp. 1406-1420.
GOST all authors (up to 50) Copy
Platt J. M., Ryvkin P., Wanat J. J., Donahue G., Ricketts M. D., Barrett S. P., Waters H. J., Song S., Chavez A., Abdallah K. O., Master S. R., Wang L., Johnson F. Rap1 relocalization contributes to the chromatin-mediated gene expression profile and pace of cell senescence // Genes and Development. 2013. Vol. 27. No. 12. pp. 1406-1420.
RIS |
Cite this
RIS Copy
TY - JOUR
DO - 10.1101/gad.218776.113
UR - https://doi.org/10.1101%2Fgad.218776.113
TI - Rap1 relocalization contributes to the chromatin-mediated gene expression profile and pace of cell senescence
T2 - Genes and Development
AU - Platt, Jesse M.
AU - Ryvkin, Paul
AU - Wanat, Jennifer J.
AU - Donahue, Greg
AU - Ricketts, M Dan
AU - Barrett, Steven P
AU - Waters, Hannah J
AU - Song, Shufei
AU - Chavez, Alejandro
AU - Abdallah, Khaled Omar
AU - Master, Stephen R.
AU - Wang, Li-San
AU - Johnson, F
PY - 2013
DA - 2013/06/11 00:00:00
PB - Cold Spring Harbor Laboratory
SP - 1406-1420
IS - 12
VL - 27
PMID - 23756653
SN - 0890-9369
SN - 1549-5477
ER -
BibTex |
Cite this
BibTex Copy
@article{2013_Platt
author = {Jesse M. Platt and Paul Ryvkin and Jennifer J. Wanat and Greg Donahue and M Dan Ricketts and Steven P Barrett and Hannah J Waters and Shufei Song and Alejandro Chavez and Khaled Omar Abdallah and Stephen R. Master and Li-San Wang and F Johnson},
title = {Rap1 relocalization contributes to the chromatin-mediated gene expression profile and pace of cell senescence},
journal = {Genes and Development},
year = {2013},
volume = {27},
publisher = {Cold Spring Harbor Laboratory},
month = {jun},
url = {https://doi.org/10.1101%2Fgad.218776.113},
number = {12},
pages = {1406--1420},
doi = {10.1101/gad.218776.113}
}
MLA
Cite this
MLA Copy
Platt, Jesse M., et al. “Rap1 relocalization contributes to the chromatin-mediated gene expression profile and pace of cell senescence.” Genes and Development, vol. 27, no. 12, Jun. 2013, pp. 1406-1420. https://doi.org/10.1101%2Fgad.218776.113.
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