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Developmentally dynamic histone acetylation pattern of a tissue-specific chromatin domain.

Forsberg, Ec Downs, Km Christensen, Hm Im, H Nuzzi, Pa Bresnick, Eh

Published in Proceedings of the National Academy of Sciences

We have defined the histone acetylation pattern of the endogenous murine beta-globin domain, which contains the erythroidspecific beta-globin genes. The beta-globin locus control region (LCR) and transcriptionally active promoters were enriched in acetylated histones in fetal liver relative to fetal brain, whereas the inactive promoters were hypoac...

Evidence for the widespread coupling of alternative splicing and nonsense-mediated mRNA decay in humans.

Lewis, Bp Green, Re Brenner, Se

Published in Proceedings of the National Academy of Sciences

To better understand the role of alternative splicing, we conducted a large-scale analysis of reliable alternative isoforms of known human genes. Each isoform was classified according to its splice pattern and supporting evidence. We found that one-third of the alternative transcripts examined contain premature termination codons, and most persist ...

Semisynthetic cytochrome c.

Barstow, Le Young, Rs Yakali, E Sharp, Jj O Brien, Jc Phil Berman Harbury, Ha

Published in Proceedings of the National Academy of Sciences

Horse heart cytochrome c can be split with cyanogen bromide into a heme peptide (residues 1-65) and a nonheme peptide (residues 66-104). In a process involving (i) complex formation between the two fragments and (ii) restoration of the severed peptide linkage, a fully active cytochrome c preparation can be re-formed. Use has been made of this proce...

Knowledge-based analysis of microarray gene expression data by using support vector machines.

Brown, Mp Grundy, Wn Lin, D Cristianini, N Sugnet, Cw Furey, Ts Ares M, Jr David Haussler

Published in Proceedings of the National Academy of Sciences

We introduce a method of functionally classifying genes by using gene expression data from DNA microarray hybridization experiments. The method is based on the theory of support vector machines (SVMs). SVMs are considered a supervised computer learning method because they exploit prior knowledge of gene function to identify unknown genes of similar...

Demographic history and rare allele sharing among human populations.

Gravel, Simon Henn, Brenna M Gutenkunst, Ryan N Indap, Amit R Marth, Gabor T Clark, Andrew G Yu, Fuli Gibbs, Richard A Bustamante, Carlos D

Published in Proceedings of the National Academy of Sciences of the United States of America

High-throughput sequencing technology enables population-level surveys of human genomic variation. Here, we examine the joint allele frequency distributions across continental human populations and present an approach for combining complementary aspects of whole-genome, low-coverage data and targeted high-coverage data. We apply this approach to da...

Targeting protein-trafficking pathways alters melanoma treatment sensitivity.

Huang, Zhi-ming Chinen, Milka Chang, Philip J Xie, Tong Zhong, Lily Demetriou, Stephanie Patel, Mira P Scherzer, Rebecca Sviderskaya, Elena V Bennett, Dorothy C ...

Published in Proceedings of the National Academy of Sciences of the United States of America

Protein-trafficking pathways are targeted here in human melanoma cells using methods independent of oncogene mutational status, and the ability to up-regulate and down-regulate tumor treatment sensitivity is demonstrated. Sensitivity of melanoma cells to cis-diaminedichloroplatinum II (cDDP, cis-platin), carboplatin, dacarbazine, or temozolomide to...

Vascular Robo4 restricts proangiogenic VEGF signaling in breast.

Marlow, R Binnewies, M Sorensen, Lk Monica, Sd Strickland, P Forsberg, Ec Li, Dy Lindsay Hinck

Published in Proceedings of the National Academy of Sciences

Formation of the vascular system within organs requires the balanced action of numerous positive and negative factors secreted by stromal and epithelial cells. Here, we used a genetic approach to determine the role of SLITs in regulating the growth and organization of blood vessels in the mammary gland. We demonstrate that vascularization of the gl...

Epigenetic characterization of hematopoietic stem cell differentiation using miniChIP and bisulfite sequencing analysis....

Attema, Jl Papathanasiou, P Forsberg, Ec Xu, J Smale, St Weissman, Il

Published in Proceedings of the National Academy of Sciences

Hematopoietic stem cells (HSC) produce all blood cell lineages by virtue of their capacity to self-renew and differentiate into progenitors with decreasing cellular potential. Recent studies suggest that epigenetic mechanisms play an important role in controlling stem cell potency and cell fate decisions. To investigate this hypothesis in HSC, we h...

Molecular mechanics of 30S subunit head rotation.

Mohan, S Donohue, Jp Harry Noller

Published in Proceedings of the National Academy of Sciences

During ribosomal translocation, a process central to the elongation phase of protein synthesis, movement of mRNA and tRNAs requires large-scale rotation of the head domain of the small (30S) subunit of the ribosome. It has generally been accepted that the head rotates by pivoting around the neck helix (h28) of 16S rRNA, its sole covalent connection...

Proton-hydroxide permeability of liposomes.

David Deamer Nichols, Jw

Published in Proceedings of the National Academy of Sciences

Liposome permeability to net proton-hydroxide flux was compared under two conditions that have produced extreme values in previous studies. In the first [Nichols, J.W. & Deamer, D.W. (1980) Proc. Natl. Acad. Sci. USA 77, 2038-2042] small pH gradients were permitted to decay near pH 7 and permeability coefficients in the range of 10(-4) cm/sec were ...

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