RESUMEN
Coronavirus 2019 (COVID-19) has caused ongoing disruptions to U.S. meat markets via demand and supply-side shocks. Abnormally high prices have been reported at retail outlets and meat packers have been accused of unfair business practices because of widening price spreads. Processing facilities have experienced COVID-19 outbreaks resulting in shutdowns. Using weekly data on wholesale and retail prices of beef, pork, and poultry, we characterize the time series behavior and dynamic linkages of U.S. meat prices before the COVID-19 pandemic. We model vertical price transmission using both linear and threshold autoregressive (AR) models and vector error correction (VEC) models. With the estimated models, we then compare price movements under COVID-19 to model predictions. All three meat markets are well-integrated and we observe unexpected, large price movements in April and May of 2020. Early COVID-19 related shocks appear to be transitory with prices returning to expected levels at a pace consistent with the speed of transmission prior to the pandemic. This well-functioning market process suggests a degree of resilience in U.S. meat supply chains.
RESUMEN
Ubiquitylation of histone H2B at lysine 120 (H2B-Ub), a post-translational modification first discovered in 1980, plays a critical role in diverse nuclear processes including the regulation of transcription and DNA damage repair. Herein, we use a suite of protein chemistry methods to explore how H2B-Ub stimulates hDot1L-mediated methylation of histone H3 on lysine 79 (H3K79me). By using semisynthetic 'designer' chromatin containing H2B-Ub bearing a site-specifically installed photocrosslinker, here we report an interaction between a functional hotspot on ubiquitin and the N-terminus of histone H2A. Our biochemical studies indicate that this interaction is required for stimulation of hDot1L activity and leads to a repositioning of hDot1L on the nucleosomal surface, which likely places the active site of the enzyme proximal to H3K79. Collectively, our data converge on a possible mechanism for hDot1L stimulation in which H2B-Ub physically 'corrals' the enzyme into a productive binding orientation.
Asunto(s)
Regulación Enzimológica de la Expresión Génica/fisiología , Histonas/metabolismo , Metiltransferasas/metabolismo , Nucleosomas , N-Metiltransferasa de Histona-Lisina , Histonas/genética , Humanos , Metilación , Metiltransferasas/genética , Modelos Moleculares , Unión Proteica , Conformación Proteica , Proteínas UbiquitinadasRESUMEN
Ubiquitylation of histone H2B at lysine 120 (H2B-Ub) plays a critical role in transcriptional elongation, chromatin conformation, as well as the regulation of specific histone H3 methylations. Herein, we report a strategy for the site-specific chemical attachment of ubiquitin to preassembled nucleosomes. This allowed expedited structure-activity studies into how H2B-Ub regulates H3K79 methylation by the methyltransferase human Dot1. Through an alanine scan of the ubiquitin surface, we identified a functional hotspot on ubiquitin that is required for the stimulation of human Dot1 in vitro. Importantly, this result was validated in chromatin from isolated nuclei by using a synthetic biology strategy that allowed selective incorporation of the hotspot-deficient ubiquitin mutant into H2B. The ubiquitin hotspot additionally impacted the regulation of ySet1-mediated H3K4 methylation but was not required for H2B-Ub-induced impairment of chromatin fiber compaction. These data demonstrate the utility of applying chemical ligation technologies to preassembled chromatin and delineate the multifunctionality of ubiquitin as a histone posttranslational modification.