Erwin Schroedinger, Francis Crick and epigenetic stability.

Schroedinger's book 'What is Life?' is widely credited for having played a crucial role in development of molecular and cellular biology. My essay revisits the issues raised by this book from the modern perspective of epigenetics and systems biology. I contrast two classes of potential mechanisms of epigenetic stability: 'epigenetic templating' and 'systems biology' approaches, and consider them from the point of view expressed by Schroedinger.

Coactivators p300 and PCAF physically and functionally interact with the foamy viral trans-activator.

Background: Foamy virus Bel1/Tas trans-activators act as key regulators of gene expression and directly bind to Bel1 response elements (BRE) in both the internal and the 5'LTR promoters leading to strong transcriptional trans-activation. Cellular coactivators interacting with Bel1/Tas are unknown to date.

Results: Transient expression assays, co-immunoprecipitation experiments, pull-down assays, and Western blot analysis were used to demonstrate that the coactivator p300 and histone acetyltransferase PCAF specifically interact with the retroviral trans-activator Bel1/Tas in vivo.

Chromatin dynamics and DNA repair.

Packing of the eukaryotic genome into chromatin poses an accessibility problem for the DNA repair machinery. Chromatin structure has to be changed for the repair to occur, and we are beginning to discover how different chromatin modifying mechanisms facilitate DNA repair in the chromatin context. On the other hand, the repair-related changes in chromatin should be transient, and a particular chromatin state should be able to survive the repair process.

Ssdp proteins interact with the LIM-domain-binding protein Ldb1 to regulate development.

The LIM-domain-binding protein Ldb1 is a key factor in the assembly of transcriptional complexes involving LIM-homeodomain proteins and other transcription factors that regulate animal development. We identified Ssdp proteins (previously described as sequence-specific, single-stranded-DNA-binding proteins) as components of Ldb1-associated nuclear complexes in HeLa cells. Ssdp proteins are associated with Ldb1 in a variety of additional mammalian cell types.

Metastable macromolecular complexes containing high mobility group nucleosome-binding chromosomal proteins in HeLa nuclei.

High mobility group nucleosome-binding (HMGN) proteins belong to a family of nuclear proteins that bind to nucleosomes and enhance transcription from chromatin templates by altering the structure of the chromatin fiber. The intranuclear organization of these proteins is dynamic and related to the metabolic state of the cell. Here we report that approximately 50% of the HMGN proteins are organized into macromolecular complexes in a fashion that is similar to that of other nuclear activities that modify the structure of the chromatin fiber.