Lineage-specific dynamic and pre-established enhancer–promoter contacts cooperate in terminal differentiation

Chromosome conformation is an important feature of metazoan gene regulation; however, enhancer–promoter contact remodeling during cellular differentiation remains poorly understood. To address this, genome-wide promoter capture Hi-C (CHi-C) was performed during epidermal differentiation. Two classes of enhancer–promoter contacts associated with differentiation-induced genes were identified. The first class ('gained') increased in contact strength during differentiation in concert with enhancer acquisition of the H3K27ac activation mark. The second class ('stable') were pre-established in undifferentiated cells, with enhancers constitutively marked by H3K27ac. The stable class was associated with the canonical conformation regulator cohesin, whereas the gained class was not, implying distinct mechanisms of contact formation and regulation. Analysis of stable enhancers identified a new, essential role for a constitutively expressed, lineage-restricted ETS-family transcription factor, EHF, in epidermal differentiation. Furthermore, neither class of contacts was observed in pluripotent cells, suggesting that lineage-specific chromatin structure is established in tissue progenitor cells and is further remodeled in terminal differentiation

5C analysis of the Epidermal Differentiation Complex locus reveals distinct chromatin interaction networks between gene-rich and gene-poor TADs in skin epithelial cells

YesMammalian genomes contain several dozens of large (>0.5 Mbp) lineage-specific gene loci harbouring functionally related genes. However, spatial chromatin folding, organization of the enhancer-promoter networks and their relevance to Topologically Associating Domains (TADs) in these loci remain poorly understood. TADs are principle units of the genome folding and represents the DNA regions within which DNA interacts more frequently and less frequently across the TAD boundary. Here, we used Chromatin Conformation Capture Carbon Copy (5C) technology to characterize spatial chromatin interaction network in the 3.1 Mb Epidermal Differentiation Complex (EDC) locus harbouring 61 functionally related genes that show lineage-specific activation during terminal keratinocyte differentiation in the epidermis. 5C data validated by 3D-FISH demonstrate that the EDC locus is organized into several TADs showing distinct lineage-specific chromatin interaction networks based on their transcription activity and the gene-rich or gene-poor status. Correlation of the 5C results with genome-wide studies for enhancer-specific histone modifications (H3K4me1 and H3K27ac) revealed that the majority of spatial chromatin interactions that involves the gene-rich TADs at the EDC locus in keratinocytes include both intra- and inter-TAD interaction networks, connecting gene promoters and enhancers. Compared to thymocytes in which the EDC locus is mostly transcriptionally inactive, these interactions were found to be keratinocyte-specific. In keratinocytes, the promoter-enhancer anchoring regions in the gene-rich transcriptionally active TADs are enriched for the binding of chromatin architectural proteins CTCF, Rad21 and chromatin remodeler Brg1. In contrast to gene-rich TADs, gene-poor TADs show preferential spatial contacts with each other, do not contain active enhancers and show decreased binding of CTCF, Rad21 and Brg1 in keratinocytes. Thus, spatial interactions between gene promoters and enhancers at the multi-TAD EDC locus in skin epithelial cells are cell type-specific and involve extensive contacts within TADs as well as between different gene-rich TADs, forming the framework for lineage-specific transcription.This study was supported by the grants 5R01AR064580 and 1RO1AR071727 to VAB, TKS and AAS, as well as by the grants from MRC (MR/ M010015/1) and BBSRC (BB/K010050/1) to VAB

Theoretical study of small silicon clusters on a graphite layer

In a series of recent experiments, the HOMO-LUMO energy gaps of small Si clusters deposited on a graphite substrate have been determined by Scanning Tunneling Microscopy (STM). The values obtained were found to be substantially smaller than the energy gaps of corresponding passivated clusters. This work considers dimensional reduction as a possible mechanism for a sizeable energy gap narrowing by the example of the system Si5. The impact of the graphite substrate on the deposited species is investigated in the framework of a pseudocluster model

Iron oxides semiconductors are efficients for solar water disinfection: A comparison with photo-Fenton processes at neutral pH

The photocatalytic activities of four different commercially available iron (hydr)oxides semiconductors, i.e. hematite (alpha-Fe2O3), goethite (alpha-FeOOH), wustite (FeO) and magnetite (Fe3O4), were evaluated for bacteria inactivation at neutral pH in the absence or presence of H2O2. Our results showed that heterogeneous photocatalysis and/or photo-Fenton processes catalyzed by low concentrations of reagents (0.6 mg/L Fe3+ and 10 mg/L H2O2) under sunlight may serve as a disinfection method for waterborne bacterial pathogens. In particular, we found that, with the exception of magnetite which need H2O2 as electron acceptor, all the other semiconductor iron (hydr)oxides were photoactive under sunlight in absence of H2O2 (using only oxygen as electron acceptor). Furthermore, for all iron (hydr)oxide studied in this work, no bacterial reactivation and/or growth was observed after photo-Fenton treatment. The same antimicrobial activity was obtained for the photocatalytic semiconducting action of hematite and goethite. Additionally, a delayed disinfection effect was observed to continue in the dark for the photo-assisted wilstite-based treatment. Electron spin resonance (ESR) in combination with spin-trapping was employed to detect reactive oxygen species (ROS) involved in heterogeneous photocatalysis and/or photo-Fenton treatments mediated by iron (hydr)oxide particles. In particular, ESR confirmed that center dot OH and O-2(center dot-) radicals were the principal ROS produced under photo-assisted action of iron (hydr)oxide particles in the absence or presence of H2O2. We also found that the components of natural water (i.e. natural organic matter (NOM) and inorganic substances) did not interfere with the photocatalytic semiconducting action of hematite to bacterial inactivation. However, these components enhance the bacterial inactivation by heterogeneous photo-Fenton action of hematite. Overall our results demonstrated, for the first time, that low concentration of iron (hydr)oxides, acting both as photocatalytic semiconductors or catalysts of the heterogeneous photo-Fenton process at neutral pH, may provide a useful strategy for efficient bacterial disinfection. (C) 2014 Elsevier B.V. All rights reserved