Michaël Bender

Bio: Michaël Bender is an academic researcher from University of Lyon. The author has contributed to research in topics: Mean field theory & Pairing. The author has an hindex of 50, co-authored 157 publications receiving 15835 citations. Previous affiliations of Michaël Bender include University of North Carolina at Chapel Hill & University of Tennessee.

Comprehensive mapping of long-range interactions reveals folding principles of the human genome.

Abstract: We describe Hi-C, a method that probes the three-dimensional architecture of whole genomes by coupling proximity-based ligation with massively parallel sequencing. We constructed spatial proximity maps of the human genome with Hi-C at a resolution of 1 megabase. These maps confirm the presence of chromosome territories and the spatial proximity of small, gene-rich chromosomes. We identified an additional level of genome organization that is characterized by the spatial segregation of open and closed chromatin to form two genome-wide compartments. At the megabase scale, the chromatin conformation is consistent with a fractal globule, a knot-free, polymer conformation that enables maximally dense packing while preserving the ability to easily fold and unfold any genomic locus. The fractal globule is distinct from the more commonly used globular equilibrium model. Our results demonstrate the power of Hi-C to map the dynamic conformations of whole genomes.

Self-consistent mean-field models for nuclear structure

Abstract: The authors review the present status of self-consistent mean-field (SCMF) models for describing nuclear structure and low-energy dynamics. These models are presented as effective energy-density functionals. The three most widely used variants of SCMF's based on a Skyrme energy functional, a Gogny force, and a relativistic mean-field Lagrangian are considered side by side. The crucial role of the treatment of pairing correlations is pointed out in each case. The authors discuss other related nuclear structure models and present several extensions beyond the mean-field model which are currently used. Phenomenological adjustment of the model parameters is discussed in detail. The performance quality of the SCMF model is demonstrated for a broad range of typical applications.

An expansive human regulatory lexicon encoded in transcription factor footprints

Abstract: Regulatory factor binding to genomic DNA protects the underlying sequence from cleavage by DNase I, leaving nucleotide-resolution footprints. Using genomic DNase I footprinting across 41 diverse cell and tissue types, we detected 45 million transcription factor occupancy events within regulatory regions, representing differential binding to 8.4 million distinct short sequence elements. Here we show that this small genomic sequence compartment, roughly twice the size of the exome, encodes an expansive repertoire of conserved recognition sequences for DNA-binding proteins that nearly doubles the size of the human cis-regulatory lexicon. We find that genetic variants affecting allelic chromatin states are concentrated in footprints, and that these elements are preferentially sheltered from DNA methylation. High-resolution DNase I cleavage patterns mirror nucleotide-level evolutionary conservation and track the crystallographic topography of protein-DNA interfaces, indicating that transcription factor structure has been evolutionarily imprinted on the human genome sequence. We identify a stereotyped 50-base-pair footprint that precisely defines the site of transcript origination within thousands of human promoters. Finally, we describe a large collection of novel regulatory factor recognition motifs that are highly conserved in both sequence and function, and exhibit cell-selective occupancy patterns that closely parallel major regulators of development, differentiation and pluripotency.

Shell structure of superheavy nuclei in self-consistent mean-field models

Abstract: We study the extrapolation of nuclear shell structure to the region of superheavy nuclei in self-consistent mean-field models[emdash]the Skyrme-Hartree-Fock approach and the relativistic mean-field model[emdash]using a large number of parametrizations which give similar results for stable nuclei but differ in detail. Results obtained with the folded-Yukawa potential which is widely used in macroscopic-macroscopic models are shown for comparison. We focus on differences in the isospin dependence of the spin-orbit interaction and the effective mass between the models and their influence on single-particle spectra. The predictive power of the mean-field models concerning single-particle spectra is discussed for the examples of [sup 208]Pb and the spin-orbit splittings of selected neutron and proton levels in [sup 16]O, [sup 132]Sn, and [sup 208]Pb. While all relativistic models give a reasonable description of spin-orbit splittings, all Skyrme interactions show a wrong trend with mass number. The spin-orbit splitting of heavy nuclei might be overestimated by 40[percent][endash]80[percent], which exposes a fundamental deficiency of the current nonrelativistic models. In most cases the occurrence of spherical shell closures is found to be nucleon-number dependent. Spherical doubly magic superheavy nuclei are found at [sub 184][sup 298]114, [sub 172][sup 292]120, or [sub 184][sup 310]126 depending on the parametrization. The Z=114more » proton shell closure, which is related to a large spin-orbit splitting of proton 2f states, is predicted only by forces which by far overestimate the proton spin-orbit splitting in [sup 208]Pb. The Z=120 and N=172 shell closures predicted by the relativistic models and some Skyrme interactions are found to be related to a central depression of the nuclear density distribution. This effect cannot appear in macroscopic-microscopic models or semiclassical approaches like the extended Thomas-Fermi-Strutinski integral approach which have a limited freedom for the density distribution only. In summary, our findings give a strong argument for [sub 172][sup 292]120 to be the next spherical doubly magic superheavy nucleus. [copyright] [ital 1999] [ital The American Physical Society]« less

Developmental and species-divergent globin switching are driven by BCL11A

Abstract: The contribution of changes in cis-regulatory elements or trans-acting factors to interspecies differences in gene expression is not well understood. The mammalian beta-globin loci have served as a model for gene regulation during development. Transgenic mice containing the human beta-globin locus, consisting of the linked embryonic (epsilon), fetal (gamma) and adult (beta) genes, have been used as a system to investigate the temporal switch from fetal to adult haemoglobin, as occurs in humans. Here we show that the human gamma-globin (HBG) genes in these mice behave as murine embryonic globin genes, revealing a limitation of the model and demonstrating that critical differences in the trans-acting milieu have arisen during mammalian evolution. We show that the expression of BCL11A, a repressor of human gamma-globin expression identified by genome-wide association studies, differs between mouse and human. Developmental silencing of the mouse embryonic globin and human gamma-globin genes fails to occur in mice in the absence of BCL11A. Thus, BCL11A is a critical mediator of species-divergent globin switching. By comparing the ontogeny of beta-globin gene regulation in mice and humans, we have shown that alterations in the expression of a trans-acting factor constitute a critical driver of gene expression changes during evolution.

I and i

Abstract: There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality. Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

An integrated encyclopedia of DNA elements in the human genome.

Abstract: The human genome encodes the blueprint of life, but the function of the vast majority of its nearly three billion bases is unknown. The Encyclopedia of DNA Elements (ENCODE) project has systematically mapped regions of transcription, transcription factor association, chromatin structure and histone modification. These data enabled us to assign biochemical functions for 80% of the genome, in particular outside of the well-studied protein-coding regions. Many discovered candidate regulatory elements are physically associated with one another and with expressed genes, providing new insights into the mechanisms of gene regulation. The newly identified elements also show a statistical correspondence to sequence variants linked to human disease, and can thereby guide interpretation of this variation. Overall, the project provides new insights into the organization and regulation of our genes and genome, and is an expansive resource of functional annotations for biomedical research.

Topological domains in mammalian genomes identified by analysis of chromatin interactions

Abstract: The spatial organization of the genome is intimately linked to its biological function, yet our understanding of higher order genomic structure is coarse, fragmented and incomplete. In the nucleus of eukaryotic cells, interphase chromosomes occupy distinct chromosome territories, and numerous models have been proposed for how chromosomes fold within chromosome territories. These models, however, provide only few mechanistic details about the relationship between higher order chromatin structure and genome function. Recent advances in genomic technologies have led to rapid advances in the study of three-dimensional genome organization. In particular, Hi-C has been introduced as a method for identifying higher order chromatin interactions genome wide. Here we investigate the three-dimensional organization of the human and mouse genomes in embryonic stem cells and terminally differentiated cell types at unprecedented resolution. We identify large, megabase-sized local chromatin interaction domains, which we term 'topological domains', as a pervasive structural feature of the genome organization. These domains correlate with regions of the genome that constrain the spread of heterochromatin. The domains are stable across different cell types and highly conserved across species, indicating that topological domains are an inherent property of mammalian genomes. Finally, we find that the boundaries of topological domains are enriched for the insulator binding protein CTCF, housekeeping genes, transfer RNAs and short interspersed element (SINE) retrotransposons, indicating that these factors may have a role in establishing the topological domain structure of the genome.