ABSTRACT The E2F transcription factor family determines whether or not a cell will divide by controlling the expression of key cell-cycle regulators. The individual E2Fs can be divided into

distinct subgroups that act in direct opposition to one another to promote either cellular proliferation or cell-cycle exit and terminal differentiation. What is the underlying molecular

basis of this 'push-me–pull-you' regulation, and what are its biological consequences? Access through your institution Buy or subscribe This is a preview of subscription content,

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REGULATORY PROGRAMS USING A SINGLE-CELL ATLAS OF MOUSE DEVELOPMENT Article 11 July 2022 THE ROLE(S) OF NF-Y IN DEVELOPMENT AND DIFFERENTIATION Article Open access 26 September 2024

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Translating the histone code. _Science_ 293, 1074–1080 (2001). Article  CAS  PubMed  Google Scholar  Download references AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Center for Cancer

Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, 02139, Massachusetts, USA Jeffrey M. Trimarchi & Jacqueline A. Lees Authors * Jeffrey M. Trimarchi

View author publications You can also search for this author inPubMed Google Scholar * Jacqueline A. Lees View author publications You can also search for this author inPubMed Google Scholar

CORRESPONDING AUTHOR Correspondence to Jacqueline A. Lees. RELATED LINKS RELATED LINKS DATABASES ENCYCLOPEDIA OF LIFE SCIENCES: cell division cycle nucleosome structures  LOCUSLINK: ATR

_B-myb_ _cdc2_ CRM1 _cyclin A2_ cyclin E dE2F2 DP1 _E2f1_ _E2f2_ _E2f3_ _E2f4_ _E2f5_ p16 p19ARF p21 p27 p107 p130 pRB RYBP SUV39H2 thymidylate synthetase  SWISS-PROT: ATM Bmi-1 CBFA1 Cdc2

Cdc6 Cdc25A Cdk2 Cdk4 Cdk6 c-myc cyclin A cyclin D1 dE2F1 dihydrofolate reductase E2F1 E2F2 E2F3 E2F4 E2F5 E2F6 HP1 Mre11 ORC1 p53 p73 PPAR-γ SUV39H1 thymidine kinase GLOSSARY * CHECKPOINT

PATHWAYS The classic definition of a checkpoint pathway/protein is one that is not required for normal cell-cycle regulation but is essential for the ability of the cell to arrest in

response to a stress condition. Frequently, this term is used less strictly to describe proteins that have a key role in cell-cycle-stress responses, regardless of their role in normal

cell-cycle regulation. * p53 The p53 transcription factor is activated in response to various stress conditions, including DNA damage. It activates various target genes that trigger either

apoptosis or cell-cycle arrest, depending on the cell type and the stress conditions. p53 is a tumour suppressor and it, or its upstream regulators, are disrupted in a large proportion of

human tumours. * CHROMATIN-IMMUNOPRECIPITATION (ChIP) ASSAYS ChIP assays can be used to monitor the association of DNA-binding proteins with specific promoters _in vivo_. Briefly, live cells

are treated with crosslinking agents to tether the proteins to the DNA. The selected protein is then recovered by immunoprecipitation, the crosslinking is reversed and the co-precipitating

DNA is screened for the enrichment of specific promoter fragments using the polymerase chain reaction (PCR). * TRANSFORMATION Transformation is the process by which a primary cell becomes a

tumour cell. It is generally characterized by a reduction in growth-factor dependence, a failure to arrest growth in response to contact inhibition, and the ability to grow in soft agar

(that is, without attachment). * PRIMARY CELLS Primary cells are cells that are derived from a living organism. They undergo a limited, predetermined number of cell divisions before

arresting permanently in G0 — a process that is called cellular senescence. * p19ARF The _p19__ARF_ gene (the human equivalent is called _p14__ARF_) is expressed from the _Ink4_ locus and

its coding sequence partially overlaps with that of _p16__INK4a_. The p19ARF protein activates p53 by binding to Mdm2 (an E3 ubiquitin ligase) and prevents it from triggering p53

degradation. * THE NBS1/MRE11 COMPLEX The _Nbs1_ gene was identified by virtue of its mutation in the inherited chromosome instability disorder Nijmegen breakage syndrome (NBS). Its protein

product, Nibrin, forms a complex with the DNA-repair proteins Mre11 and Rad50. This complex seems to have an important role in recombinational DNA repair, replication and the activation of a

DNA-damage induced S-phase checkpoint. * POLYCOMB COMPLEX _Polycomb (Pc)_ was identified as a dominant mutation in _Drosophila_ that led to the presence of sex combs on the second and third

legs of male flies instead of only the first leg. The _Drosophila_ polycomb group (PcG) includes several genes that yield similar homeotic transformation phenotypes when mutated. Their

protein products associate with one another to form at least two possible Polycomb complexes. These maintain the repression of _hox_ gene expression, which is essential for embryonic

patterning. The PcG also exists in mammals, but seems much more complex. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Trimarchi, J., Lees, J. Sibling

rivalry in the E2F family. _Nat Rev Mol Cell Biol_ 3, 11–20 (2002). https://doi.org/10.1038/nrm714 Download citation * Issue Date: 01 January 2002 * DOI: https://doi.org/10.1038/nrm714 SHARE

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