Chromatin unfolding by Cdt1 regulates MCM loading via opposing functions of HBO1 and HDAC11-geminin.

The efficiency of metazoan origins of DNA replication is known to be enhanced by histone acetylation near origins. Although this correlates with increased MCM recruitment, the mechanism by which such acetylation regulates MCM loading is unknown. We show here that Cdt1 induces large-scale chromatin decondensation that is required for MCM recruitment.

A role for E2F activities in determining the fate of Myc-induced lymphomagenesis.

The phenotypic heterogeneity that characterizes human cancers reflects the enormous genetic complexity of the oncogenic process. This complexity can also be seen in mouse models where it is frequently observed that in addition to the initiating genetic alteration, the resulting tumor harbors additional, somatically acquired mutations that affect the tumor phenotype. To investigate the role of genetic interactions in the development of tumors, we have made use of the Emu-myc model of pre-B and B cell lymphoma.

Acetylation/deacetylation modulates the stability of DNA replication licensing factor Cdt1.

Proper expression of the replication licensing factor Cdt1 is primarily regulated post-translationally by ubiquitylation and proteasome degradation. In a screen to identify novel non-histone targets of histone deacetylases (HDACs), we found Cdt1 as a binding partner for HDAC11. Cdt1 associates specifically and directly with HDAC11.

Bok, Bcl-2-related Ovarian Killer, Is Cell Cycle-regulated and Sensitizes to Stress-induced Apoptosis.

Bok/Mtd (Bcl-2-related ovarian killer/Matador) is considered a pro-apoptotic member of the Bcl-2 family. Although identified in 1997, little is known about its biological role. We have previously demonstrated that Bok mRNA is up-regulated following E2F1 overexpression.

Acetylation and deacetylation of non-histone proteins.

Since the first report of p53 as a non-histone target of a histone acetyltransferase (HAT), there has been a rapid proliferation in the description of new non-histone targets of HATs. Of these, transcription factors comprise the largest class of new targets. The substrates for HATs extend to cytoskeletal proteins, molecular chaperones and nuclear import factors.

Trapping and characterization of novel retinoid response elements.

Retinoids, such as retinoic acid (RA), play a critical role in normal vertebrate development and physiology. However, embryonic exposure to excess retinoids also causes severe malformations. Retinoids bind RA receptors and retinoid X receptors, thus activating a plethora of genes.