Biology subjects

Shoemaker, L.

Publications and source records attributed to Shoemaker, L..

3 recordsLinked to original sources

bioRxiv2024

SATB2 and circ3915 RNA chromatin dysregulation drive KRAS-like oncogenic transformation

Even though epigenetic factors contribute to oncogenesis, most human cancer models still assume that disease originates from driver DNA mutations. Thus, it is still unclear if non-genetic mechanisms are sufficient to trigger malignant transformation. Special AT-rich binding protein 2 (SATB2) is a chromatin organizer that brings distal DNA elements into close proximity, thus remodeling chromatin structures to reprogram cell-specific and/or developmentally-sensitive gene networks. Here, we discover that SATB2 generates a co-expressed circ3915 RNA that is translated into a peptide and co-locates with SATB2 in the cell nucleus. Ectopic SATB2 or circ3915 over- expression rearranges global chromatin accessibility, generates KRAS- and NFE2L2-like oncogenic gene expression patterns, and transforms lung epithelial cells independent of driver mutations. Thus, oncogenic pathways can be activated in mammalian cells without pre-disposing mutations in oncogenes or epigenetic regulators. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=153 SRC="FIGDIR/small/616681v1_ufig1.gif" ALT="Figure 1000"> View larger version (32K): org.highwire.dtl.DTLVardef@1314b69org.highwire.dtl.DTLVardef@14df9e1org.highwire.dtl.DTLVardef@505bddorg.highwire.dtl.DTLVardef@1bf3fab_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

bioRxiv2024

Age-dependent Changes in a Chaperone Complex in the Mouse Heart

The exquisitely organized sarcomere, the unit of contraction of striated muscle, is a stable structure with slow turnover of its components. The myosin chaperone UNC-45 and its binding partners, Hsp90 and Hsp70, are required for the initial folding of the myosin head domain and the assembly of myosin into thick filaments. There is increasing evidence that the UNC-45 system has an important role during aging to preserve sarcomere organization. Its decline may be a key factor in sarcopenia. Unlike skeletal muscle, the UNC-45 system in cardiac muscle in aging heart has not been examined extensively. Here we show that Unc45b and Hsp70 are localized to sarcomeric Z-discs in the mouse heart. We further show that during aging, there is a decline in the levels of myosin heavy chain, Unc-45b and Hsp70, but not Hsp90. While the decrease in Unc45b appears to be at the mRNA level, the decrease in the levels of myosin and Hsp70 were not at the mRNA but at the protein level. We have reported that in skeletal muscle, there is a decline in both Unc45b and Hsp90, and here we show that there is no such decline of Hsp70 in skeletal muscle. Hsp70 levels also did not decline with age in the brain or the liver. This heart-specific decrease of Hsp70 through its function as an Unc45b/Hsp70 complex might account for the age-dependent worsening of cardiomyopathies, and through Hsp70s multiple Unc-45b-independent functions, affect the folding and assembly of many other proteins in the aging heart.

cell biology↗

bioRxiv2020

The Internal Structure of Metacommunities

Current analyses of metacommunity data largely focus on global attributes across the entire metacommunity, such as mean alpha, beta, and gamma diversity, as well as the partitioning of compositional variation into single estimates of contributions of space and environmental effects and, more recently, possible contributions of species interactions. However, this view neglects the fact that different species and sites in the landscape can vary widely in how they contribute to these metacommunity-wide attributes. We argue for a new conceptual framework with matched analytics with the goals of studying the complex and interactive relations between process and pattern in metacommunities that is focused on the variation among species and among sites which we call the internal structure of the metacommunity. To demonstrate how the internal structure could be studied, we create synthetic data using a process-based colonization-extinction metacommunity model. We then use Joint Species Distribution Models to estimate how the contributions of space, environment and biotic interactions driving metacommunity assembly differ among species and sites. We find that this approach to the internal structure of metacommunities provides useful information about the distinct ways that different species and different sites contribute to metacommunity structure. Although it has limitations, our work points at a more general approach to understand how other possible complexities might affect internal structure and might thus be incorporated into a more cohesive metacommunity theory.

ecology↗