TNF Regulates the In Vivo Occupancy of Both Distal and Proximal Regulatory Regions of the MCP-1/JE Gene

AbstractIn vivo genomic footprinting (IVGF) was used to examine regulatory site occupancy during the activation of the murine inflammatory response gene MCP-1/JE by TNF. In response to TNF, both promoter distal and proximal regulatory regions became occupied in vivo. EMSA analysis showed that while some of the factors involved in expression, including NF-κB, were translocated to the nucleus following TNF treatment, others were already present and able to bind DNA in vitro. Protein kinase inhibitor studies showed that protein phosphorylation was required for TNF activation but not factor assembly. These studies provide evidence for a multistep model of TNF-mediated gene regulation involving chromatin accessibility, transcription factor complex assembly, and protein phosphorylation

The insulator factor CTCF controls MHC class II gene expression and is required for the formation of long-distance chromatin interactions

Knockdown of the insulator factor CCCTC binding factor (CTCF), which binds XL9, an intergenic element located between HLA-DRB1 and HLA-DQA1, was found to diminish expression of these genes. The mechanism involved interactions between CTCF and class II transactivator (CIITA), the master regulator of major histocompatibility complex class II (MHC-II) gene expression, and the formation of long-distance chromatin loops between XL9 and the proximal promoter regions of these MHC-II genes. The interactions were inducible and dependent on the activity of CIITA, regulatory factor X, and CTCF. RNA fluorescence in situ hybridizations show that both genes can be expressed simultaneously from the same chromosome. Collectively, the results suggest a model whereby both HLA-DRB1 and HLA-DQA1 loci can interact simultaneously with XL9, and describe a new regulatory mechanism for these MHC-II genes involving the alteration of the general chromatin conformation of the region and their regulation by CTCF

Vector radiative transfer model for coupled atmosphere and ocean systems including inelastic sources in ocean waters

Inelastic scattering plays an important role in ocean optics. The main inelastic scattering mechanisms include Raman scattering, fluorescence by colored dissolved organic matter (FDOM), and fluorescence by chlorophyll. This paper reports an implementation of all three inelastic scattering mechanisms in the exact vector radiative transfer model for coupled atmosphere and ocean Systems (CAOS). Simulation shows that FDOM contributes to the water radiation field in the broad visible spectral region, while chlorophyll fluorescence is limited in a narrow band centered at 685 nm. This is consistent with previous findings in the literature. The fluorescence distribution as a function of depth and viewing angle is presented. The impacts of fluorescence to the degree of linear polarization (DoLP) and orientation of the polarization ellipse (OPE) are studied. The DoLP is strongly influenced by inelastic scattering at wavelengths with strong inelastic scattering contribution. The OPE is less affected by inelastic scattering but it has a noticeable impact, in terms of the angular region of positive polarization, in the backward direction. This effect is more apparent for deeper water depth

Balancing Selection on a Regulatory Region Exhibiting Ancient Variation That Predates Human–Neandertal Divergence

Ancient population structure shaping contemporary genetic variation has been recently appreciated and has important implications regarding our understanding of the structure of modern human genomes. We identified a ∼36-kb DNA segment in the human genome that displays an ancient substructure. The variation at this locus exists primarily as two highly divergent haplogroups. One of these haplogroups (the NE1 haplogroup) aligns with the Neandertal haplotype and contains a 4.6-kb deletion polymorphism in perfect linkage disequilibrium with 12 single nucleotide polymorphisms (SNPs) across diverse populations. The other haplogroup, which does not contain the 4.6-kb deletion, aligns with the chimpanzee haplotype and is likely ancestral. Africans have higher overall pairwise differences with the Neandertal haplotype than Eurasians do for this NE1 locus (p<10−15). Moreover, the nucleotide diversity at this locus is higher in Eurasians than in Africans. These results mimic signatures of recent Neandertal admixture contributing to this locus. However, an in-depth assessment of the variation in this region across multiple populations reveals that African NE1 haplotypes, albeit rare, harbor more sequence variation than NE1 haplotypes found in Europeans, indicating an ancient African origin of this haplogroup and refuting recent Neandertal admixture. Population genetic analyses of the SNPs within each of these haplogroups, along with genome-wide comparisons revealed significant FST (p = 0.00003) and positive Tajima's D (p = 0.00285) statistics, pointing to non-neutral evolution of this locus. The NE1 locus harbors no protein-coding genes, but contains transcribed sequences as well as sequences with putative regulatory function based on bioinformatic predictions and in vitro experiments. We postulate that the variation observed at this locus predates Human–Neandertal divergence and is evolving under balancing selection, especially among European populations

An Overview of Approaches and Challenges for Retrieving Marine Inherent Optical Properties from Ocean Color Remote Sensing

Ocean color measured from satellites provides daily global, synoptic views of spectral water-leaving reflectances that can be used to generate estimates of marine inherent optical properties (IOPs). These reflectances, namely the ratio of spectral upwelled radiances to spectral downwelled irradiances, describe the light exiting a water mass that defines its color. IOPs are the spectral absorption and scattering characteristics of ocean water and its dissolved and particulate constituents. Because of their dependence on the concentration and composition of marine constituents, IOPs can be used to describe the contents of the upper ocean mixed layer. This information is critical to further our scientific understanding of biogeochemical oceanic processes, such as organic carbon production and export, phytoplankton dynamics, and responses to climatic disturbances. Given their importance, the international ocean color community has invested significant effort in improving the quality of satellite-derived IOP products, both regionally and globally. Recognizing the current influx of data products into the community and the need to improve current algorithms in anticipation of new satellite instruments (e.g., the global, hyperspectral spectroradiometer of the NASA Plankton, Aerosol, Cloud, ocean Ecosystem (PACE) mission), we present a synopsis of the current state of the art in the retrieval of these core optical properties. Contemporary approaches for obtaining IOPs from satellite ocean color are reviewed and, for clarity, separated based their inversion methodology or the type of IOPs sought. Summaries of known uncertainties associated with each approach are provided, as well as common performance metrics used to evaluate them. We discuss current knowledge gaps and make recommendations for future investment for upcoming missions whose instrument characteristics diverge sufficiently from heritage and existing sensors to warrant reassessing current approaches

An Overview of Approaches and Challenges for Retrieving Marine Inherent Optical Properties from Ocean Color Remote Sensing

Ocean color measured from satellites provides daily global, synoptic views of spectral water-leaving reflectancesthat can be used to generate estimates of marine inherent optical properties (IOPs). These reflectances, namelythe ratio of spectral upwelled radiances to spectral downwelled irradiances, describe the light exiting a watermass that defines its color. IOPs are the spectral absorption and scattering characteristics of ocean water and itsdissolved and particulate constituents. Because of their dependence on the concentration and composition ofmarine constituents, IOPs can be used to describe the contents of the upper ocean mixed layer. This informationis critical to further our scientific understanding of biogeochemical oceanic processes, such as organic carbonproduction and export, phytoplankton dynamics, and responses to climatic disturbances. Given their im-portance, the international ocean color community has invested significant effort in improving the quality of satellite-derived IOP products, both regionally and globally. Recognizing the current influx of data products intothe community and the need to improve current algorithms in anticipation of new satellite instruments (e.g., theglobal, hyperspectral spectroradiometer of the NASA Plankton, Aerosol, Cloud, ocean Ecosystem (PACE) mis-sion), we present a synopsis of the current state of the art in the retrieval of these core optical properties.Contemporary approaches for obtaining IOPs from satellite ocean color are reviewed and, for clarity, separatedbased their inversion methodology or the type of IOPs sought. Summaries of known uncertainties associated witheach approach are provided, as well as common performance metrics used to evaluate them. We discuss currentknowledge gaps and make recommendations for future investment for upcoming missions whose instrumentcharacteristics diverge sufficiently from heritage and existing sensors to warrant reassessing current approaches

Multiple Histone Methyl and Acetyltransferase Complex Components Bind the HLA-DRA Gene

Major histocompatibility complex class II (MHC-II) genes are fundamental components that contribute to adaptive immune responses. While characterization of the chromatin features at the core promoter region of these genes has been studied, the scope of histone modifications and the modifying factors responsible for activation of these genes are less well defined. Using the MHC-II gene HLA-DRA as a model, the extent and distribution of major histone modifications associated with active expression were defined in interferon-γ induced epithelial cells, B cells, and B-cell mutants for MHC-II expression. With active transcription, nucleosome density around the proximal regulatory region was diminished and histone acetylation and methylation modifications were distributed throughout the gene in distinct patterns that were dependent on the modification examined. Irrespective of the location, the majority of these modifications were dependent on the binding of either the X-box binding factor RFX or the class II transactivator (CIITA) to the proximal regulatory region. Importantly, once established, the modifications were stable through multiple cell divisions after the activating stimulus was removed, suggesting that activation of this system resulted in an epigenetic state. A dual crosslinking chromatin immunoprecipitation method was used to detect histone modifying protein components that interacted across the gene. Components of the MLL methyltransferase and GCN5 acetyltransferase complexes were identified. Some MLL complex components were found to be CIITA independent, including MLL1, ASH2L and RbBP5. Likewise, GCN5 containing acetyltransferase complex components belonging to the ATAC and STAGA complexes were also identified. These results suggest that multiple complexes are either used or are assembled as the gene is activated for expression. Together the results define and illustrate a complex network of histone modifying proteins and multisubunit complexes participating in MHC-II transcription