Premature senescence in human melanocytes after exposure to solar UVR: An exosome and UV-miRNA connection.

Ultraviolet radiation (UVR) can play two roles: induce cellular senescence and convert skin melanocytes into melanoma. To assess whether this conversion might rely on melanocytes having to first acquire a senescent phenotype, we studied the effects of physiological doses of UVR (UVA + UVB) on quiescent melanocytes in vitro. Repeated doses of UVR induced these melanocytes into a senescent-like state.

The dynamics of E1A in regulating networks and canonical pathways in quiescent cells.

Background: Adenoviruses force quiescent cells to re-enter the cell cycle to replicate their DNA, and for the most part, this is accomplished after they express the E1A protein immediately after infection. In this context, E1A is believed to inactivate cellular proteins (e.g.

E1A interacts with two opposing transcriptional pathways to induce quiescent cells into S phase.

Despite data suggesting that the adenovirus E1A protein of 243 amino acids creates an S-phase environment in quiescent cells by overcoming the nucleosomal repression of E2F-regulated genes, the precise mechanisms underlying E1A's ability in this process have not yet been defined at the biochemical level. In this study, we show by kinetic analysis that E1A, as opposed to an E1A mutant failing to bind p130, can temporally eliminate corepressor complexes consisting of p130-E2F4 and HDAC1/2-mSin3B from the promoters of E2F-regulated genes in quiescent cells. Once the complexes are removed, the di-methylation of H3K9 at these promoters becomes dramatically diminished, and this in turn allows for the acetylation of H3K9/14 and the recruitment of activating E2F family members, which is then followed by the transcriptional activity of the E2F-regulated genes.

Activation of Cdc6 by MyoD is associated with the expansion of quiescent myogenic satellite cells.

MyoD is a transcriptional factor that is required for the differentiation of muscle stem cells (satellite cells). In this study, we describe a previously unknown function for MyoD in regulating a gene (Cdc6) that is vital to endowing chromatin with the capability of replicating DNA. In C2C12 and primary mouse myoblasts, we show that MyoD can occupy an E-box within the promoter of Cdc6 and that this association, along with E2F3a, is required for its activity.

A viral mechanism for remodeling chromatin structure in G0 cells.

Small DNA viruses force quiescent cells to reenter the cell cycle in order to replicate their DNA. We report here that the adenovirus E1A protein creates an S phase environment in quiescent cells by overcoming the nucleosomal repression of E2F-targeted genes. These genes are surrounded by Lys-9-methylated H3 histones, and their promoters are occupied by the pRb-related protein p130 and the inhibitory transcription factor E2F4.

MyoD is functionally linked to the silencing of a muscle-specific regulatory gene prior to skeletal myogenesis.

Most of the genes that are central to the process of skeletal muscle differentiation remain in a transcriptionally silent or "off" state until muscle cells (myoblasts) are induced to differentiate. Although the mechanisms that contribute to this phenomenon are still unclear, it is likely that histone deacetylases (HDACs), which play an important role in the repression of genes, are principally involved. Recent studies indicate that the initiator of the myogenic program, namely MyoD, can associate with the deacetylase HDAC1 in vivo, and because HDACs are usually recruited to promoters by specific proteins, we considered the possibility that these two proteins might be acting together at the promoters of muscle-specific genes to repress their transcription in myoblasts.