AP-1 imprints a reversible transcriptional program of senescent cells

Senescent cells affect many physiological and pathophysiological processes. While select genetic and epigenetic elements for senescence induction have been identified, the dynamics, epigenetic mechanisms and regulatory networks defining senescence competence, induction and maintenance remain poorly understood, precluding the deliberate therapeutic targeting of senescence for health benefits. Here, we examined the possibility that the epigenetic state of enhancers determines senescent cell fate. We explored this by generating time-resolved transcriptomes and epigenome profiles during oncogenic RAS-induced senescence and validating central findings in different cell biology and disease models of senescence. Through integrative analysis and functional validation, we reveal links between enhancer chromatin, transcription factor recruitment and senescence competence. We demonstrate that activator protein 1 (AP-1) ‘pioneers’ the senescence enhancer landscape and defines the organizational principles of the transcription factor network that drives the transcriptional programme of senescent cells. Together, our findings enabled us to manipulate the senescence phenotype with potential therapeutic implications

Recent results in relativistic heavy ion collisions: from ``a new state of matter'' to "the perfect fluid"

Experimental Physics with Relativistic Heavy Ions dates from 1992 when a beam of 197Au of energy greater than 10A GeV/c first became available at the Alternating Gradient Synchrotron (AGS) at Brookhaven National Laboratory (BNL) soon followed in 1994 by a 208Pb beam of 158A GeV/c at the Super Proton Synchrotron (SPS) at CERN (European Center for Nuclear Research). Previous pioneering measurements at the Berkeley Bevalac in the late 1970's and early 1980's were at much lower bombarding energies (~ 1 A GeV/c) where nuclear breakup rather than particle production is the dominant inelastic process in A+A collisions. More recently, starting in 2000, the Relativistic Heavy Ion Collider (RHIC) at BNL has produced head-on collisions of two 100A GeV beams of fully stripped Au ions, corresponding to nucleon-nucleon center-of-mass energy, sqrt(sNN)=200 GeV, total c.m. energy 200A GeV. The objective of this research program is to produce nuclear matter with extreme density and temperature, possibly resulting in a state of matter where the quarks and gluons normally confined inside individual nucleons (r < 1 fm) are free to act over distances an order of magnitude larger. Progress from the period 1992 to the present will be reviewed, with reference to previous results from light ion and proton-proton collisions where appropriate. Emphasis will be placed on the measurements which formed the basis for the announcements by the two major laboratories: "A new state of matter", by CERN on Feb 10, 2000 and "The perfect fluid", by BNL on April 19, 2005.Comment: 62 pages, 39 figures. Review article published in Reports on Progress in Physics on June 23, 2006. In this published version, mistakes, typographical errors, and citations have been corrected and a subsection has been adde