Estrogen receptor is a nuclear receptor superfamily member of transcriptional activators that regulate gene expression by recruiting diverese transcriptional coregulators. The Mediator complex is a central transcriptional coactivator complex that acts as a bridge between transcriptional activators and RNA polymerase II. MED1 (Mediator subunit 1) is the key Mediator subunit that directly interacts with estrogen receptor to mediate its functions both in vitro and in vivo. Interestingly, our previous biochemical analyses indicated that MED1 exists only in a subpopulation of the Mediator complex that is enriched with a number of distinct Mediator subunits and RNA polymerase II. Here, we report ARGLU1 as a MED1/Mediator-associated protein. We found that ARGLU1 (arginine and glutamate rich 1) not only colocalizes with MED1 in the nucleus, but also directly interacts with a far C-terminal region of MED1. Reporter assays indicate that ARGLU1 is able to cooperate with MED1 to regulate estrogen receptor-mediated gene transcription. Importantly, ARGLU1 is recruited, in a ligand-dependent manner, to endogenous estrogen receptor target gene promoters and is required for their expression. Furthermore, by ChIP-reChIP assay, we confirm that ARGLU1 and MED1 colocalize on the same estrogen receptor target gene promoter upon estrogen induction. Moreover, we found that depletion of ARGLU1 significantly impairs the growth, as well as anchorage-dependent and -independent colony formation of breast cancer cells. Taken together, these results establish ARGLU1 as a new MED1-interacting protein required for estrogen-dependent gene transcription and breast cancer cell growth.Estrogen receptor belongs to a nuclear receptor superfamily of transcriptional activators that, in a ligand-dependent manner, regulates the expression of specific genes controlling the development, reproduction, homeostasis, and metabolism of an organism (1, 2). Like other nuclear receptors, estrogen receptor shares a common organization of functional domains: a highly variable N-terminal activation function-1 domain that mediates ligand-independent transcription, a highly conserved central DNA-binding domain that specifically binds to hormone-response elements in cognate promoters of target genes, and a moderately conserved C-terminal ligand-binding domain containing activation domain 2, which mediates ligand-dependent transcription (1, 2). Upon ligand binding, the ultimate action of these receptors on regulating target gene expression is to enhance the recruitment and/or function of the general transcriptional machinery, including RNA polymerase II and general transcription factors (3-6). In the past decades, increasingly diverse groups of transcriptional coregulators have been found to play key roles in this process (3, 4). Among them, Mediator has emerged as a key transcriptional coregulator complex that is responsible for communicating the signals from transcription activators to RNA polymerase II and the general transcription machinery (7-9).Mediator is a large ...

Tan sheep (Ovis aries), a Chinese indigenous breed, has special curly fleece after birth, especially at one month old. However, this unique phenotype disappears gradually with age and the underlying reasons of trait evolvement are still unknown. In this study, skin transcriptome data was used to study this issue. In total 51,215 transcripts including described transcripts and transfrags were identified. Pathway analysis of the top 100 most highly expressed transcripts, which included TCHH and keratin gene family members, such as KRT25, KRT5, KRT71, KRT14 and others, showed pathways known to be relevant to hair/fleece development and function. Six hundred differentially expressed (DE) transcripts were detected at two different physiological ages (one-month-old with curly fleece and 48-month-old without curly fleece) and were categorized into three major functional groups: cellular component, molecular function, and biological process. The top six functional categories included cell, cell part, cellular process, binding, intracellular, metabolic process. The detected differentially expressed genes were particularly involved in signal, signal peptide, disulfide bond, glycoprotein and secreted terms, respectively. Further splicing isoform analysis showed that the metallothionein 3 isoform was up-regulated in Tan lamb skin, indicating that it may be related to the conformation of curly fleece in Chinese Tan lamb. The hair-related important differentially expressed genes (SPINK4, FGF21, ESRα, EphA3, NTNG1 and GPR110) were confirmed by qPCR analysis. We deduced that the differences existed in expressed transcripts, splice isoforms and GO categories between the two different physiological stages, which might constitute the major reasons for explaining the trait evolvement of curly fleece in Chinese Tan sheep. This study provides some clues for elucidating the molecular mechanism of fleece change with age in Chinese Tan sheep, as well as supplying some potential values for understanding human hair disorder and texture changes.

Some surface reactions of interest to electrocatalysis in alkaline media are promoted by crystalline defects, while others occur preferentially on defect-free terraces. Different forms of structure sensitivity, and the underlying causes of this structure sensitivity, have been examined using several fuel-cell-relevant surface reactions in alkaline media as model reactions. Oxidation of CO serves as a model for defect favored reactions, while reduction of oxygen serves as a model for terrace favored reactions. More complicated reactions, such as methanol oxidation, can be interpreted as containing multiple steps that are either defect favored or terrace favored. The role of defects in each of these reactions was interpreted in terms of geometric and electronic effects, with different types of defects ͑kink type and step type͒ showing different effects for the different electrocatalytic processes. CO oxidation is promoted by both step-type and kink-type defects, as a result of electronic structure, but methanol dehydrogenation is promoted only by step-type defects, as a result of geometric structure.

Single-atom catalysts (SACs) with atomic dispersion and coordinated unsaturated active sites have sparked gigantic attention, focusing on high activity, selectivity, atom utilization, and a unique metal−support coordination environment. However, isolated single atoms possess high surface free energy, especially under harsh reaction conditions, and tend to migrate and agglomerate into clusters or nanoparticles in an elusive manner. Herein, we have integrated different types of N-doped carbon (N-C) materials as Lewis base sites to anchor dispersed metal atoms. The lone pairs of electrons donated by N-rich materials effectively resist metal sintering. The matrix includes organic compounds, MOFs, N-doped graphene, g-C 3 N 4 , and biomass. Furthermore, we also emphasized the application of N-C material-based SACs in ORR, OER, HER, organic reactions, and CO 2 RR. Beneficially, these establish a definitive correlation between construction strategy and catalytic performance. Finally, we review the staged challenges and development opportunities confronted by SACs and pave the way for balancing the electronic structure and catalytic properties of SACs supported on derived N-C materials.