The Transcription Factor ThPOK Orchestrates Stochastic Interchromosomal Interactions Required for IFNB1 Virus-Inducible Gene Expression.

Virus infection induces stochastic activation of the interferon-ß gene. Three previously identified Alu-like DNA elements called NRCs (NF-κB reception centers) function by capturing and delivering NF-κB to the IFNB1 enhancer via stochastic interchromosomal interactions. We show that the transcription factor ThPOK binds cooperatively with NF-κB to NRCs and mediates their physical proximity with the IFNB1 gene via its ability to oligomerize when bound to DNA. ThPOK knockdown significantly decreased the frequency of interchromosomal interactions, NF-κB DNA binding to the IFNB1 enhancer, and virus-induced IFNB1 gene activation. We also demonstrate that cooperative DNA binding between ThPOK and NF-κB on the same face of the double DNA helix is required for interchromosomal interactions and distinguishes NRCs from various other Alu elements bearing κB sites. These studies show how DNA binding cooperativity of stereospecifically aligned transcription factors provides the necessary ultrasensitivity for the all-or-none stochastic cell responses to virus infection.

A novel SATB1 protein isoform with different biophysical properties.

Intra-thymic T cell development is coordinated by the regulatory actions of SATB1 genome organizer. In this report, we show that SATB1 is involved in the regulation of transcription and splicing, both of which displayed deregulation in Satb1 knockout murine thymocytes. More importantly, we characterized a novel SATB1 protein isoform and described its distinct biophysical behavior, implicating potential functional differences compared to the commonly studied isoform. SATB1 utilized its prion-like domains to transition through liquid-like states to aggregated structures. This behavior was dependent on protein concentration as well as phosphorylation and interaction with nuclear RNA. Notably, the long SATB1 isoform was more prone to aggregate following phase separation. Thus, the tight regulation of SATB1 isoforms expression levels alongside with protein post-translational modifications, are imperative for SATB1's mode of action in T cell development. Our data indicate that deregulation of these processes may also be linked to disorders such as cancer.

A novel use of the caesium-137 technique to estimate human interference and historical water level in a Mediterranean Temporary Pond.

The sustainability of, and the effects of human pressures on, Omalos Mediterranean Temporary Pond (MTP), Chanea, Greece was assessed. The (137)Cs technique was used to identify alleged anthropogenic interference (excavation) in the studied area. It was found that about one third of the ponds bed surface material had been removed and disposed of on the northeast edge, confirming unplanned excavations that took place in the MTP area some years ago. Nonetheless, five years after the excavation, the MTP's ecosystem (flora and fauna) had recovered, which indicates that these small ecosystems are resilient to direct human pressures, like excavations. Moreover, with the (137)Cs technique it was possible to identify the historical water level of Omalos MTP, when the fallout from the Chernobyl accident reached this area, in May of 1986. Therefore, the (137)Cs technique can be useful in the identification of the historical water level of small MTPs and other ephemeral water bodies. Applications include the verification and validation of hydrological models.