The tumor suppressor gene hypermethylated in cancer 1 is transcriptionally regulated by E2F1.

The Hypermethylated in Cancer 1 (HIC1) gene encodes a zinc finger transcriptional repressor that cooperates with p53 to suppress cancer development. We and others recently showed that HIC1 is a transcriptional target of p53. To identify additional transcriptional regulators of HIC1, we screened a set of transcription factors for regulation of a human HIC1 promoter reporter.

Bypass of senescence by the polycomb group protein CBX8 through direct binding to the INK4A-ARF locus.

The Polycomb group (PcG) proteins are essential for embryogenesis, and their expression is often found deregulated in human cancer. The PcGs form two major protein complexes, called polycomb repressive complexes 1 and 2 (PRC1 and PRC2) whose function is to maintain transcriptional repression. Here, we demonstrate that the chromodomain-containing protein, CBX8, which is part of one of the PRC1 complexes, regulates proliferation of diploid human and mouse fibroblasts through direct binding to the INK4A-ARF locus.

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.

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.

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.