No abstract

Cell signaling pathways that control proliferation and determine cell fates are tightly regulated to prevent developmental anomalies and cancer. Transcription factors and coregulators are important effectors of signaling pathway output, as they regulate downstream gene programs. In Caenorhabditis elegans, several subunits of the Mediator transcriptional coregulator complex promote or inhibit vulva development, but pertinent mechanisms are poorly defined. Here, we show that Mediator's dissociable cyclin dependent kinase 8 (CDK8) module (CKM), consisting of cdk-8, cic-1/Cyclin C, mdt-12/dpy-22, and mdt-13/let-19, is required to inhibit ectopic vulval cell fates downstream of the epidermal growth factor receptor (EGFR)-Ras-extracellular signal-regulated kinase (ERK) pathway. cdk-8 inhibits ectopic vulva formation by acting downstream of mpk-1/ERK, cell autonomously in vulval cells, and in a kinasedependent manner. We also provide evidence that the CKM acts as a corepressor for the Ets-family transcription factor LIN-1, as cdk-8 promotes transcriptional repression by LIN-1. In addition, we find that CKM mutation alters Mediator subunit requirements in vulva development: the mdt-23/sur-2 subunit, which is required for vulva development in wild-type worms, is dispensable for ectopic vulva formation in CKM mutants, which instead display hallmarks of unrestrained Mediator tail module activity. We propose a model whereby the CKM controls EGFR-Ras-ERK transcriptional output by corepressing LIN-1 and by fine tuning Mediator specificity, thus balancing transcriptional repression vs. activation in a critical developmental signaling pathway. Collectively, these data offer an explanation for CKM repression of EGFR signaling output and ectopic vulva formation and provide the first evidence of Mediator CKM-tail module subunit crosstalk in animals.KEYWORDS Mediator complex; CDK8; MED23; MED15; EGFR; Notch P RECISE regulation of transcription is required to execute developmental programs such as proliferation and cell fate determination. The Mediator complex ("Mediator") is a conserved eukaryotic transcriptional coregulator of RNA polymerase II (Pol II) transcription (Malik and Roeder 2010;Poss et al. 2013). Mediator consists of 30 subunits that assemble into four modules. "Core" Mediator consists of three of the four modules: the head and middle modules, which contact Pol II, and the tail module, which serves as a docking site for transcription factors. The fourth module, the dissociable cyclin dependent kinase 8 (CDK8) kinase module (CKM), interacts with transcription factors, core Mediator, chromatin, and the Pol II machinery to either repress or activate transcription (Malik and Roeder 2010;Nemet et al. 2014 transcription, tail and CKM subunits regulate specific transcriptional programs in animal development or physiology (Malik and Roeder 2010;Nemet et al. 2014). The CKM consists of enzymatic subunits CDK8 and cyclin C, and structural subunits MED12 and MED13 that tether the CKM to core Mediator (Tsai et al. 2013). C...

A comprehensive transcript index of the human genome generated using microarrays and computational approaches This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. A comprehensive transcript index of the human genome generated using microarrays and computational approaches

Computational and microarray-based experimental approaches were used to generate a comprehensive transcript index for the human genome. Oligonucleotide probes designed from approximately 50,000 known and predicted transcript sequences from the human genome were used to survey transcription from a diverse set of 60 tissues and cell lines using ink-jet microarrays. Further, expression activity over at least six conditions was more generally assessed using genomic tiling arrays consisting of probes tiled through a repeat-masked version of the genomic sequence making up chromosomes 20 and 22.

In the present work, the single buffer layers of La 2 Zr 2 O 7 (LZO) with different thicknesses were prepared using pulsed laser deposition (PLD) on highly textured Ni-5 at.%W tapes for YBa 2 Cu 3 O 7−δ -coated conductors. The highly textured LZO layers are obtained on the metallic substrates, making the subsequent epitaxial growth of superconducting YBa 2 Cu 3 O 7−δ layers feasible. The superconducting transition temperature increases as the LZO thickness increases up to 240 nm, achieving a value of T c of more than 92 K with a narrow transition width less than 1 K. Inductive measurement reveals that the critical current density (J c ) reaches 0.77 MA cm −2 at 77 K in self-field, showing that the single buffer of LZO is comparable to standard buffer architectures such as CeO 2 /YSZ/Y 2 O 3 or CeO 2 /LZO. This implies that the LZO as a single buffer layer is promising for the simplification of the preparation process, leading to cost-effective coated conductors.

No abstract

No abstract

No abstract

No abstract