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Biomedical subjects

Emmanuelle Trinh

Publications and source records attributed to Emmanuelle Trinh.

4 recordsLinked to original sources
PubMed2005

Characterization of E2F8, a novel E2F-like cell-cycle regulated repressor of E2F-activated transcription.

The E2F family of transcription factors are downstream effectors of the retinoblastoma protein, pRB, pathway and are essential for the timely regulation of genes necessary for cell-cycle progression. Here we describe the characterization of human and murine E2F8, a new member of the E2F family. Sequence analysis of E2F8 predicts the presence of two distinct E2F-related DNA binding domains suggesting that E2F8 and, the recently, identified E2F7 form a subgroup within the E2F family. We show that E2F transcription factors bind the E2F8 promoter in vivo and that expression of E2F8 is being induced at the G1/S transition. Purified recombinant E2F8 binds specifically to a consensus E2F-DNA-binding site indicating that E2F8, like E2F7, binds DNA without the requirement of co-factors such as DP1. E2F8 inhibits E2F-driven promoters suggesting that E2F8 is transcriptional repressor like E2F7. Ectopic expression of E2F8 in diploid human fibroblasts reduces expression of E2F-target genes and inhibits cell growth consistent with a role for repressing E2F transcriptional activity. Taken together, these data suggest that E2F8 has an important role in turning of the expression of E2F-target genes in the S-phase of the cell cycle.

Amino Acid Sequence↗
PubMed2004

Naturally death-resistant precursor cells revealed as the origin of retinoblastoma.

The molecular mechanisms and the cell-of-origin leading to retinoblastoma are not well defined. In this issue of Cancer Cell, Bremner and colleagues describe the first inheritable model of retinoblastoma, revealing that loss of the pocket proteins pRb and p107 deregulates cell cycle exit in retinal precursors. The authors show that a subset of these precursors contain an inherent resistance to apoptosis, and that while most terminally differentiate, some are likely to acquire additional mutations, leading to tumor formation. Thus, this work defines the cell-of-origin of retinoblastoma and suggests that mutations giving increased proliferative capacity are required for retinoblastoma development.

Alleles↗
PubMed2003

Selective E2F-dependent gene transcription is controlled by histone deacetylase activity during neuronal apoptosis.

The alteration of chromatin through histone acetylation and deacetylation participates in the regulation of gene expression. We have investigated the effects of histone deacetylase inhibition on neuronal fate. We show that treatment of primary neurones with trichostatin A (TSA) or sodium butyrate (NaBu) induces typical features of apoptosis, a cell death that relies on specific genetic programmes. We have further explored the molecular mechanisms implicated in the TSA response and demonstrated that TSA-induced apoptosis is partly dependent on the activation of the transcription factor E2F-1, which has pro-apoptotic functions in these neurones. Furthermore, the increased e2f-1 transcriptional response is probably the result of mechanisms occurring through E2F-responsive elements. Histone acetylation also takes place at the e2f-1 promoter, but this modification is neither required nor by itself sufficient to induce increased transcription at the e2f-1 promoter. Activation might thus occur through acetylation of non-histone proteins binding this regulatory element. Finally, we show that TSA induces the transcription of E2F-dependent genes, such as its cell cycle target cyclin E, but also pro-apoptotic genes, such as Apaf1. Taken together, our results suggest that, in neuroprotective conditions, histone deacetylase activity allows a constitutive repression of the e2f-1 gene in mature neurones in order to ensure survival. Deregulation of this repression will ultimately lead to an E2F-dependent cell death.

Acetylation↗