Inter-MAR Association Contributes to Transcriptionally Active Looping Events in Human β-globin Gene Cluster

Matrix attachment regions (MARs) are important in chromatin organization and gene regulation. Although it is known that there are a number of MAR elements in the β-globin gene cluster, it is unclear that how these MAR elements are involved in regulating β-globin genes expression. Here, we report the identification of a new MAR element at the LCR(locus control region) of human β-globin gene cluster and the detection of the inter-MAR association within the β-globin gene cluster. Also, we demonstrate that SATB1, a protein factor that has been implicated in the formation of network like higher order chromatin structures at some gene loci, takes part in β-globin specific inter-MAR association through binding the specific MARs. Knocking down of SATB1 obviously reduces the binding of SATB1 to the MARs and diminishes the frequency of the inter-MAR association. As a result, the ACH establishment and the α-like globin genes and β-like globin genes expressions are affected either. In summary, our results suggest that SATB1 is a regulatory factor of hemoglobin genes, especially the early differentiation genes at least through affecting the higher order chromatin structure

Overcoming barriers to membrane protein structure determination

After decades of slow progress, the pace of research on membrane protein structures is beginning to quicken thanks to various improvements in technology, including protein engineering and microfocus X-ray diffraction. Here we review these developments and, where possible, highlight generic new approaches to solving membrane protein structures based on recent technological advances. Rational approaches to overcoming the bottlenecks in the field are urgently required as membrane proteins, which typically comprise ~30% of the proteomes of organisms, are dramatically under-represented in the structural database of the Protein Data Bank.

New amphiphiles to handle membrane proteins: "ménage à trois" between chemistry, physical chemistry and biochemistry.

International audienceTo perform biochemical and structural studies of membrane proteins (MPs), amphiphilic molecules that mimic the hydrophobic environment of lipids are required. Over the past decades, detergents, a particular class of amphiphiles, have been the most widely used for MP study. However, detergents tend to be inactivating for MPs, which has prompted the recent design of alternative strategies. The present review focuses on fluorinated amphiphiles, also called fluorinated surfactants, whose hydrophobic tail is partially fluorinated. Fluorinated chains are lipophobic, bulkier, and more rigid than the hydrogenated ones. In consequence, fluorinated surfactants (F-surfactants) would poorly interfere with protein–protein, protein–lipid, and protein–cofactor interactions, thus contributing to the stability of solubilized MPs. Here, we first introduce the concepts motivating the exploration of different F-surfactant families. We then focus on the design and the surface and self-aggregation properties of two recent series—including some original compounds—of F-surfactants bearing branched polar heads. The promising biochemical applications of F-surfactants, from the literature from 2010, are reviewed. Finally, we provide an overview of other recently developed nonconventional amphiphiles with sugar-based head groups