Analysis of promoter binding by the E2F and pRB families in vivo: distinct E2F proteins mediate activation and repression.

By Yasuhiko Takahashi, Joseph B. Rayman, B. Dynlacht. Genes & Development, 2000

676 citations recorded by the source corpus.

The E2F transcription factor plays a pivotal role in the timely activation of gene expression during mammalian cell cycle progression, whereas pRB and related proteins control cell growth in part through the ability to block the action of E2F. To identify physiologically important E2F-responsive promoters and to study their occupancy and histone acetylation state in vivo, we have taken advantage of a cross-linking approach in synchronized, living cells. We find that the pattern of E2F and pRB-related polypeptides recruited to these promoters changes in a strikingly dynamic fashion as cells progress from quiescence into G(1) and S phase: Repression of each promoter in quiescent cells is associated with recruitment of E2F-4 and p130 and low levels of histone acetylation, but by late G(1), these proteins are replaced largely by E2F-1 and E2F-3, in concert with acetylation of histones H3 and H4 and gene activation. These findings suggest that repression and activation of E2F-responsive genes may occur through distinct E2F heterodimers that direct the sequential recruitment of enzymes able to deacetylate and then acetylate core histones.

Subfields: Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/7ac95e398cd4cf6741f279a629182d400167236d

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Molecular Biology

In Oncology

Citations in the corpus

Cell cycle regulation: p53-p21-RB signaling (2022, background): “No E2F binding was observed in S phase [70].”
Control of Mitochondrial Transcription Specificity Factors (TFB1M and TFB2M) by Nuclear Respiratory Factors (NRF-1 and NRF-2) and PGC-1 Family Coactivators (2005, positive): “ification of an established method (30).”
Runx2 and Runx3 are essential for chondrocyte maturation, and Runx2 regulates limb growth through induction of Indian hedgehog. (2004, neutral): “ChIP was performed as described (Takahashi et al. 2000).”
A multigenic program mediating breast cancer metastasis to bone. (2003, methodology): “…horse anti-mouse IgG (Vector Laboratories, Inc) was used at 1:500 dilution Chromatin immunoprecipitation assayfor 30 min, followed by avidin-biotin complex (Vector Laboratories, Inc) at ChIP assays were carried out as described (Takahashi et al., 2000) using1:25 dilution and 30 min incubation.”
Rb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence. (2003, neutral): “Although Rb is often linked to normal cell cycle progresWe focused on E2F-target promoters because these sion, recent reports indicate that p107 and p130 are the genes are essential for cell cycle progression and are predominant Rb family members bound to E2F responnegatively regulated by the Rb fam”
E2Fs regulate the expression of genes involved in differentiation, development, proliferation, and apoptosis. (2001, result): “Our findings are consistent with a recent report that showed that the different E2Fs bind to the promoter region in the same gene in vivo; however, they do so at distinct times during the cell cycle (Takahashi et al. 2000).”
E2F integrates cell cycle progression with DNA repair, replication, and G(2)/M checkpoints. (2002, methodology): “as described previously (Takahashi et al. 2000), except that the cesium chloride purification step was omitted.”
The E2F family: specific functions and overlapping interests (2004, background): “Indeed, the predominant complex associated with human E2F target promoters in G0 is E2F4/p130, which is replaced by E2F4/ p107 and not by a pRB-containing E2F complex as cells reenter the cell cycle (Takahashi et al, 2000).”