ALBERT

Description: Much of euchromatin regulation occurs through reversible methylation of histone H3 lysine-4 and lysine-36 (H3K4me and H3K36me). Using the budding yeast Saccharomyces cerevisiae , we previously found that levels of H3K4me modulated temperature sensitive alleles of the transcriptional elongation complex Spt6 - Spn1 through an unknown H3K4me effector pathway. Here we identify the Rpd3S histone deacetylase complex as the H3K4me effector underlying these Spt6 - Spn1 genetic interactions. Exploiting these Spt6 - Spn1 genetic interactions, we show that H3K4me and H3K36me collaboratively impact Rpd3S function in an opposing manner. H3K36me is deposited by the histone methyltransferase Set2 and is known to promote Rpd3S function at RNA PolII transcribed open reading frames. Using genetic epistasis experiments, we find that mutations perturbing the Set2-H3K36me-Rpd3S pathway suppress the growth defects caused by temperature sensitive alleles of SPT6 and SPN1 , illuminating that this pathway antagonizes Spt6 - Spn1 . Using these sensitive genetic assays, we also identify a role for H3K4me in antagonizing Rpd3S that functions through the Rpd3S subunit Rco1 , which is known to bind H3 N-terminal tails in a manner that is prevented by H3K4me. Further genetic experiments reveal that the H3K4 and H3K36 demethylases JHD2 and RPH1 mediate this combinatorial control of Rpd3S. Finally, our studies also show that the Rpd3L complex, which acts at promoter-proximal regions of PolII transcribed genes, counters Rpd3S for genetic modulation of Spt6 - Spn1 , and that these two Rpd3 complexes balance the activities of each other. Our findings present the first evidence that H3K4me and H3K36me act combinatorially to control Rpd3S.

Description: Set1 and Jhd2 regulate the methylation state of histone H3 lysine-4 (H3K4me) through their opposing methyltransferase and demethylase activities in the budding yeast Saccharomyces cerevisiae . H3K4me associates with actively transcribed genes and, like both SET1 and JHD2 themselves, is known to regulate gene expression diversely. It remains unclear, however, if Set1 and Jhd2 act solely through H3K4me. Relevantly, Set1 methylates lysine residues in the kinetochore protein Dam1 while genetic studies of the S. pombe SET1 ortholog suggest the existence of non-H3K4 Set1 targets relevant to gene regulation. We interrogated genetic interactions of JHD2 and SET1 with essential genes involved in varied aspects of the transcription cycle. Our findings implicate JHD2 in genetic inhibition of the histone chaperone complexes Spt16 - Pob3 (FACT) and Spt6 - Spn1 . This targeted screen also revealed that JHD2 inhibits the Nrd1 - Nab3 - Sen1 (NNS) transcription termination complex. We find that while Jhd2 ’s impact on these transcription regulatory complexes likely acts via H3K4me, Set1 governs the roles of FACT and NNS through opposing H3K4-dependent and -independent functions. We also identify diametrically opposing consequences for mutation of H3K4 to alanine or arginine, illuminating that caution must be taken in interpreting histone mutation studies. Unlike FACT and NNS, detailed genetic studies suggest an H3K4me-centric mode of Spt6 - Spn1 regulation by JHD2 and SET1 . Chromatin immunoprecipitation and transcript quantification experiments show that Jhd2 opposes the positioning of a Spt6 -deposited nucleosome near the transcription start site of SER3 , a Spt6 - Spn1 regulated gene, leading to hyper-induction of SER3 . In addition to confirming and extending an emerging role for Jhd2 in the control of nucleosome occupancy near transcription start sites, our findings suggest some of the chromatin regulatory functions of Set1 are independent of H3K4 methylation.

Description: Vector-borne diseases are responsible for 〉 1 million deaths every year but genomic resources for most species responsible for their transmission are limited. This is true for neglected diseases such as sleeping sickness (Human African Trypanosomiasis), a disease caused by Trypanosoma parasites vectored by several species of tseste flies within the genus Glossina . We describe an integrative approach that identifies statistical associations between trypanosome infection status of Glossina fuscipes fuscipes ( Gff ) flies from Uganda, for which functional studies are complicated because the species cannot be easily maintained in laboratory colonies, and ~73,000 polymorphic sites distributed across the genome. Then, we identify candidate genes involved in Gff trypanosome susceptibility by taking advantage of genomic resources from a closely related species, G. morsitans morsitans ( Gmm ). We compiled a comprehensive transcript library from 72 published and unpublished RNAseq experiments of trypanosome-infected and uninfected Gmm flies, and improved the current Gmm transcriptome assembly. This new assembly was then used to enhance the functional annotations on the Gff genome. As a consequence, we identified 56 candidate genes in the vicinity of the 18 regions associated with Trypanosoma infection status in Gff . Twenty-nine of these genes were differentially expressed (DE) among parasite-infected and uninfected Gmm , suggesting that their orthologs in Gff may correlate with disease transmission. These genes were involved in DNA regulation, neurophysiological functions, and immune responses. We highlight the power of integrating population and functional genomics from related species to enhance our understanding of the genetic basis of physiological traits, particularly in nonmodel organisms.

Description: As a part of the IGAC (International Global Atmospheric Chemistry) Mega-cities program, aerosol physical and optical properties were continuously measured from March 2007 to March 2008 at an urban site (37.57° N, 126.94° E) in Seoul, Korea. Spectral optical properties of long-range transported Asian dust and pollution aerosols have been investigated based on the year long measurement data. Optically measured black carbon/thermally measured elemental carbon (BC/EC) ratio showed clear monthly variation with high values in summer and low values in winter mainly due to the enhancement of light attenuation by the internal mixing of EC. Novel approach has been suggested to retrieve the spectral light absorption coefficient (babs) from Aethalometer raw data by using BC/EC ratio. Mass absorption efficiency, σabs (=babs/EC) at 550 nm was determined to be 9.0±1.3, 8.9±1.5, 9.5±2.0, and 10.3±1.7 m2 g−1 in spring, summer, fall, and winter, respectively with an annual mean of 9.4±1.8 m2 g−1. Threshold values to classify severe haze events were suggested in this study. Increasing trend of aerosol single scattering albedo (SSA) with wavelength was observed during Asian dust events while little spectral dependence of SSA was observed during long-range transport pollution (LTP) events. Satellite aerosol optical thickness (AOT) and Hysplit air mass backward trajectory analyses as well as chemical analysis were performed to characterize the dependence of spectral optical properties on aerosol type. Results from this study can provide useful information for studies on regional air quality and aerosol's effects on climate change.

Description: As a part of the IGAC (International Global Atmospheric Chemistry) Mega-cities program, aerosol physical and optical properties were continuously measured from March 2007 to March 2008 at an urban site (37.57° N, 126.94° E) in Seoul, Korea. Spectral optical properties of long-range transported Asian dust and pollution aerosols have been investigated based on the year long measurement data. Optically measured black carbon/thermally measured elemental carbon (BC/EC) ratio showed clear monthly variation with high values in summer and low values in winter mainly due to the enhancement of light attenuation by the internal mixing of EC. Novel approach has been suggested to retrieve the spectral light absorption coefficient (babs) from Aethalometer raw data by using BC/EC ratio. Mass absorption efficiency, σabs(=babs/EC) at 550 nm at the measurement site was determined to be 9.0±1.3, 8.9±1.5, 9.5±2.0, and 10.3±1.7 m2 g−1 in spring, summer, fall, and winter, respectively with an annual mean of 9.4±1.8 m2 g−1. Threshold values to classify severe haze events were suggested in this study. Increasing trend of aerosol single scattering albedo (SSA) with wavelength was observed during Asian dust events while little spectral dependence of SSA was observed during long-range transport pollution (LTP) events. Satellite aerosol optical thickness (AOT) and Hysplit air mass backward trajectory analyses as well as chemical analysis were performed to characterize the dependence of spectral optical properties on aerosol type. Results from this study can provide useful information for studies on regional air quality and aerosol's effects on climate change.

Description: Based on two summer spatio-temporal data sets obtained from the northern South China Sea shelf and basin, this study reveals contrast relationships among bacterial production (BP), dissolved organic (DOC) and primary production (PP) in the transition zone from the neritic to the oceanic regions. Inside the mid-shelf where inorganic nutrient supplies from river discharge and internal waves were potentially abundant, BP, DOC and PP were positively inter-correlated, whereas these three measurements became uncorrelated in the oligotrophic outer-shelf and slope. A previously proposed malfunctioning microbial-loop hypothesis was extended to address the availability of limiting mineral could affect the couplings/de-couplings between the source (i.e. phytoplankton) and sink (i.e. bacteria) of biogenic organic carbon, and thus DOC dynamics. The positive correlation of the BP/PP ratios vs. phosphate concentrations in the inner-shelf implies that if anthropogenic mineral loading keeps increasing in the foreseeable future, the near-shore zone may become more heterotrophic rendering the system a stronger source of CO2.

Description: Based on two summer spatio-temporal data sets obtained from the northern South China Sea shelf and basin, this study reveals contrasting relationships among bacterial production (BP), dissolved organic (DOC) and primary production (PP) in the transition zone from the neritic to the oceanic regions. Inside the mid-shelf (bottom depth 100 days in the outer shelf, indicating that riverine (Pearl River) DOC might be more labile. The actual mechanism for this is unknown, but might relate to higher inorganic nutrient supply from river/terrestrial sources. The positive correlation of the BP / PP ratios vs. phosphate (and nitrate) concentrations in the inner shelf implies that if anthropogenic mineral loading keeps increasing in the foreseeable future, the near-shore zone may become more heterotrophic, rendering the system a stronger source of CO2.