CTCF-mediated transcriptional regulation through cell type-specific chromosome organization in the {\beta}-globin locus

The principles underlying the architectural landscape of chromatin beyond the nucleosome level in living cells remains largely unknown despite its potential to play a role in mammalian gene regulation. We investigated the 3-dimensional folding of a 1 Mbp region of human chromosome 11 containing the {\beta}-globin genes by integrating looping interactions of the insulator protein CTCF determined comprehensively by chromosome conformation capture (3C) into a polymer model of chromatin. We find that CTCF-mediated cell type specific interactions in erythroid cells are organized to favor contacts known to occur in vivo between the {\beta}-globin locus control region (LCR) and genes. In these cells, the modeled {\beta}-globin domain folds into a globule with the LCR and the active globin genes on the periphery. By contrast, in non-erythroid cells, the globule is less compact with few but dominant CTCF interactions driving the genes away from the LCR. This leads to a decrease in contact frequencies that can exceed 1000-fold depending on the stiffness of the chromatin and the exact positioning of the genes. Our findings show that an ensemble of CTCF contacts functionally affects spatial distances between control elements and target genes contributing to chromosomal organization required for transcription.Comment: Full article, including Supp. Mat., is available at Nucleic Acids Research, doi: 10.1093/nar/gks53

Initial conditions, Discreteness and non-linear structure formation in cosmology

In this lecture we address three different but related aspects of the initial continuous fluctuation field in standard cosmological models. Firstly we discuss the properties of the so-called Harrison-Zeldovich like spectra. This power spectrum is a fundamental feature of all current standard cosmological models. In a simple classification of all stationary stochastic processes into three categories, we highlight with the name ``super-homogeneous'' the properties of the class to which models like this, with $P(0)=0$, belong. In statistical physics language they are well described as glass-like. Secondly, the initial continuous density field with such small amplitude correlated Gaussian fluctuations must be discretised in order to set up the initial particle distribution used in gravitational N-body simulations. We discuss the main issues related to the effects of discretisation, particularly concerning the effect of particle induced fluctuations on the statistical properties of the initial conditions and on the dynamical evolution of gravitational clustering.Comment: 28 pages, 1 figure, to appear in Proceedings of 9th Course on Astrofundamental Physics, International School D. Chalonge, Kluwer, eds N.G. Sanchez and Y.M. Pariiski, uses crckapb.st pages, 3 figure, ro appear in Proceedings of 9th Course on Astrofundamental Physics, International School D. Chalonge, Kluwer, Eds. N.G. Sanchez and Y.M. Pariiski, uses crckapb.st

Insights into the role of DNA methylation in diatoms by genome-wide profiling in Phaeodactylum tricornutum

DNA cytosine methylation is a widely conserved epigenetic mark in eukaryotes that appears to have critical roles in the regulation of genome structure and transcription. Genome-wide methylation maps have so far only been established from the supergroups Archaeplastida and Unikont. Here we report the first whole-genome methylome from a stramenopile, the marine model diatom Phaeodactylum tricornutum. Around 6% of the genome is intermittently methylated in a mosaic pattern. We find extensive methylation in transposable elements. We also detect methylation in over 320 genes. Extensive gene methylation correlates strongly with transcriptional silencing and differential expression under specific conditions. By contrast, we find that genes with partial methylation tend to be constitutively expressed. These patterns contrast with those found previously in other eukaryotes. By going beyond plants, animals and fungi, this stramenopile methylome adds significantly to our understanding of the evolution of DNA methylation in eukaryotes.Fil: Veluchamy, Alaguraj. Institut de Biologie de l'École Normale Supérieure; FranciaFil: Lin, Xin. Institut de Biologie de l'École Normale Supérieure; Francia. Xiamen University; ChinaFil: Maumus, Florian.Fil: Rivarola, Maximo Lisandro.Fil: Bhavsar, Jaysheel.Fil: Creasy, Todd.Fil: O'Brien, Kimberly.Fil: Sengamalay, Naomi A..Fil: Tallon, Luke J..Fil: Smith, Andrew D..Fil: Rayko, Edda.Fil: Ahmed, Ikhlak.Fil: Crom, Stéphane Le.Fil: Farrant, Gregory K..Fil: Sgro, Jean-Yves.Fil: Olson, Sue A..Fil: Bondurant, Sandra Splinter.Fil: Allen, Andrew.Fil: Rabinowicz, Pablo D..Fil: Sussman, Michael R..Fil: Bowler, Chris.Fil: Tirichine, Leïla

Quantitative analysis of chromatin interaction changes upon a 4.3 Mb deletion at mouse 4E2

BACKGROUND: Circular chromosome conformation capture (4C) has provided important insights into three dimensional (3D) genome organization and its critical impact on the regulation of gene expression. We developed a new quantitative framework based on polymer physics for the analysis of paired-end sequencing 4C (PE-4Cseq) data. We applied this strategy to the study of chromatin interaction changes upon a 4.3 Mb DNA deletion in mouse region 4E2. RESULTS: A significant number of differentially interacting regions (DIRs) and chromatin compaction changes were detected in the deletion chromosome compared to a wild-type (WT) control. Selected DIRs were validated by 3D DNA FISH experiments, demonstrating the robustness of our pipeline. Interestingly, significant overlaps of DIRs with CTCF/Smc1 binding sites and differentially expressed genes were observed. CONCLUSIONS: Altogether, our PE-4Cseq analysis pipeline provides a comprehensive characterization of DNA deletion effects on chromatin structure and function

Heatshield for Extreme Entry Environment Technology (HEEET) for Missions to Saturn and Beyond

This poster provides an overview of the requirements, design, development and testing of the 3D Woven TPS being developed under NASAs Heatshield for Extreme Entry Environment Technology (HEEET) project. Under this current program, NASA is working to develop a Thermal Protection System (TPS) capable of surviving entry into Saturn. A primary goal of the project is to build and test an Engineering Test Unit (ETU) to establish a Technical Readiness Level (TRL) of 6 for this technology by 2017

Heatshield for Extreme Entry Environment Technology (HEEET) - Enabling Missions Beyond Heritage Carbon Phenolic

This poster provides an overview of the requirements, design, development and testing of the 3D Woven TPS being developed under NASA's Heatshield for Extreme Entry Environment Technology (HEEET) project. Under this current program, NASA is working to develop a Thermal Protection System (TPS) capable of surviving entry into Venus or Saturn. A primary goal of the project is to build and test an Engineering Test Unit (ETU) to establish a Technical Readiness Level (TRL) of 6 for this technology by 2017

Genetic determinants of co-accessible chromatin regions in activated T cells across humans.

Over 90% of genetic variants associated with complex human traits map to non-coding regions, but little is understood about how they modulate gene regulation in health and disease. One possible mechanism is that genetic variants affect the activity of one or more cis-regulatory elements leading to gene expression variation in specific cell types. To identify such cases, we analyzed ATAC-seq and RNA-seq profiles from stimulated primary CD4+ T cells in up to 105 healthy donors. We found that regions of accessible chromatin (ATAC-peaks) are co-accessible at kilobase and megabase resolution, consistent with the three-dimensional chromatin organization measured by in situ Hi-C in T cells. Fifteen percent of genetic variants located within ATAC-peaks affected the accessibility of the corresponding peak (local-ATAC-QTLs). Local-ATAC-QTLs have the largest effects on co-accessible peaks, are associated with gene expression and are enriched for autoimmune disease variants. Our results provide insights into how natural genetic variants modulate cis-regulatory elements, in isolation or in concert, to influence gene expression

Constraints on the shapes of galaxy dark matter haloes from weak gravitational lensing

We study the shapes of galaxy dark matter haloes by measuring the anisotropy of the weak gravitational lensing signal around galaxies in the second Red-sequence Cluster Survey (RCS2). We determine the average shear anisotropy within the virial radius for three lens samples: all galaxies with 19<m_r'<21.5, and the `red' and `blue' samples, whose lensing signals are dominated by massive low-redshift early-type and late-type galaxies, respectively. To study the environmental dependence of the lensing signal, we separate each lens sample into an isolated and clustered part and analyse them separately. We also measure the azimuthal dependence of the distribution of physically associated galaxies around the lens samples. We find that these satellites preferentially reside near the major axis of the lenses, and constrain the angle between the major axis of the lens and the average location of the satellites to =43.7 deg +/- 0.3 deg for the `all' lenses, =41.7 deg +/- 0.5 deg for the `red' lenses and =42.0 deg +/- 1.4 deg for the `blue' lenses. For the `all' sample, we find that the anisotropy of the galaxy-mass cross-correlation function =0.23 +/- 0.12, providing weak support for the view that the average galaxy is embedded in, and preferentially aligned with, a triaxial dark matter halo. Assuming an elliptical Navarro-Frenk-White (NFW) profile, we find that the ratio of the dark matter halo ellipticity and the galaxy ellipticity f_h=e_h/e_g=1.50+1.03-1.01, which for a mean lens ellipticity of 0.25 corresponds to a projected halo ellipticity of e_h=0.38+0.26-0.25 if the halo and the lens are perfectly aligned. For isolated galaxies of the `all' sample, the average shear anisotropy increases to =0.51+0.26-0.25 and f_h=4.73+2.17-2.05, whilst for clustered galaxies the signal is consistent with zero. (abridged)Comment: 28 pages, 23 figues, accepted for publication in A&

Heatshield for Extreme Entry Environment Technology (HEEET) Enabling Missions Beyond Heritage Carbon Phenolic

This poster provides an overview of the requirements, design, development and testing of the 3D Woven TPS being developed under NASAs Heatshield for Extreme Entry Environment Technology (HEEET) project. Under this current program, NASA is working to develop a Thermal Protection System (TPS) capable of surviving entry into Venus or Saturn. A primary goal of the project is to build and test an Engineering Test Unit (ETU) to establish a Technical Readiness Level (TRL) of 6 for this technology by 2017

Heatshield for Extreme Entry Environment Technology (HEEET) Enabling Missions Beyond Heritage Carbon Phenolic

Future NASA robotic missions utilizing an entry system into Venus and the outer planets, results in extremely high entry conditions that exceed the capabilities of state of the art low to mid density ablators such as PICA or AVCOAT. Previously, mission planners had to assume the use of fully dense carbon phenolic heatshields similar to what was flown on Pioneer Venus or Galileo. Carbon phenolic is a robust TPS material, however, its high density and relatively high thermal conductivity constrain mission planners to steep entries, with high heat fluxes and pressures and short entry durations. The high entry conditions pose challenges for certification in existing ground based test facilities and the longer-term sustainability of CP will continue to pose challenges. NASA has decided to invest in new technology development rather than invest in reviving carbon phenolic. The HEEET project, funded by STMD is maturing a game changing Woven Thermal Protection System technology. HEEET is a capability development project and is not tied to a single mission or destination, therefore, it is challenging to complete ground testing needed to demonstrate a capability that is much broader than any single mission or destination would require. This presentation will status HEEET progress. Near term infusion target for HEEET is the upcoming New Frontiers (NF-4) class of competitively selected Science Mission Directorate (SMD) missions for which it is incentivized