Single-Cell Exome Sequencing and Monoclonal Evolution of a JAK2-Negative Myeloproliferative Neoplasm

Single-Cell Exome Sequencing and Monoclonal Evolution of a JAK2-Negative Myeloproliferative Neoplasm:

Yong Hou, Luting Song, Ping Zhu, Bo Zhang, Ye Tao, Xun Xu, Fuqiang Li, Kui Wu, Jie Liang, Di Shao, Hanjie Wu, Xiaofei Ye, Chen Ye, Renhua Wu, Min Jian, Yan Chen, Wei Xie, Ruren Zhang, Lei Chen, Xin Liu, Xiaotian Yao, Hancheng Zheng, Chang Yu, Qibin Li, Zhuolin Gong, Mao Mao, Xu Yang, Lin Yang, Jingxiang Li, Wen Wang, Zuhong Lu, Ning Gu, Goodman Laurie, Lars Bolund, Karsten Kristiansen, Jian Wang, Huanming Yang, Yingrui Li, Xiuqing Zhang, Jun Wang. Tumor heterogeneity presents a challenge for inferring clonal evolution and driver gene identification. Here, we describe a method for analyzing the cancer genome at a single-cell nucleotide level....

Single-Cell Exome Sequencing Reveals Single-Nucleotide Mutation Characteristics of a Kidney Tumor

Single-Cell Exome Sequencing Reveals Single-Nucleotide Mutation Characteristics of a Kidney Tumor:

Xun Xu, Yong Hou, Xuyang Yin, Li Bao, Aifa Tang, Luting Song, Fuqiang Li, Shirley Tsang, Kui Wu, Hanjie Wu, Weiming He, Liang Zeng, Manjie Xing, Renhua Wu, Hui Jiang, Xiao Liu, Dandan Cao, Guangwu Guo, Xueda Hu, Yaoting Gui, Zesong Li, Wenyue Xie, Xiaojuan Sun, Min Shi, Zhiming Cai, Bin Wang, Meiming Zhong, Jingxiang Li, Zuhong Lu, Ning Gu, Xiuqing Zhang, Laurie Goodman, Lars Bolund, Jian Wang, Huanming Yang, Karsten Kristiansen, Michael Dean, Yingrui Li, Jun Wang. Clear cell renal cell carcinoma (ccRCC) is the most common kidney cancer and has very few mutations that are shared between different patients. To better understand the intratumoral genetics under....

Akirin Links Twist-Regulated Transcription with the Brahma Chromatin Remodeling Complex during Embryogenesis

Akirin Links Twist-Regulated Transcription with the Brahma Chromatin Remodeling Complex during Embryogenesis:
by Scott J. Nowak, Hitoshi Aihara, Katie Gonzalez, Yutaka Nibu, Mary K. Baylies

The activities of developmentally critical transcription factors are regulated via interactions with cofactors. Such interactions influence transcription factor activity either directly through protein–protein interactions or indirectly by altering the local chromatin environment. Using a yeast double-interaction screen, we identified a highly conserved nuclear protein, Akirin, as a novel cofactor of the key Drosophila melanogaster mesoderm and muscle transcription factor Twist. We find that Akirin interacts genetically and physically with Twist to facilitate expression of some, but not all, Twist-regulated genes during embryonic myogenesis. akirin mutant embryos have muscle defects consistent with altered regulation of a subset of Twist-regulated genes. To regulate transcription, Akirin colocalizes and genetically interacts with subunits of the Brahma SWI/SNF-class chromatin remodeling complex. Our results suggest that, mechanistically, Akirin mediates a novel connection between Twist and a chromatin remodeling complex to facilitate changes in the chromatin environment, leading to the optimal expression of some Twist-regulated genes during Drosophila myogenesis. We propose that this Akirin-mediated link between transcription factors and the Brahma complex represents a novel paradigm for providing tissue and target specificity for transcription factor interactions with the chromatin remodeling machinery.

[Report] Condition-Dependent Transcriptome Reveals High-Level Regulatory Architecture in Bacillus subtilis

[Report] Condition-Dependent Transcriptome Reveals High-Level Regulatory Architecture in Bacillus subtilis: A horizontal analysis reveals the breadth of genes turned on and off as nutrients change.

Authors: Pierre Nicolas, Ulrike Mäder, Etienne Dervyn, Tatiana Rochat, Aurélie Leduc, Nathalie Pigeonneau, Elena Bidnenko, Elodie Marchadier, Mark Hoebeke, Stéphane Aymerich, Dörte Becher, Paola Bisicchia, Eric Botella, Olivier Delumeau, Geoff Doherty, Emma L. Denham, Mark J. Fogg, Vincent Fromion, Anne Goelzer, Annette Hansen, Elisabeth Härtig, Colin R. Harwood, Georg Homuth, Hanne Jarmer, Matthieu Jules, Edda Klipp, Ludovic Le Chat, François Lecointe, Peter Lewis, Wolfram Liebermeister, Anika March, Ruben A. T. Mars, Priyanka Nannapaneni, David Noone, Susanne Pohl, Bernd Rinn, Frank Rügheimer, Praveen K. Sappa, Franck Samson, Marc Schaffer, Benno Schwikowski, Leif Steil, Jörg Stülke, Thomas Wiegert, Kevin M. Devine, Anthony J. Wilkinson, Jan Maarten van Dijl, Michael Hecker, Uwe Völker, Philippe Bessières, Philippe Noirot

[Report] Global Network Reorganization During Dynamic Adaptations of Bacillus subtilis Metabolism

[Report] Global Network Reorganization During Dynamic Adaptations of Bacillus subtilis Metabolism: A vertical analysis reveals that a simple switch of one food for another evokes changes at many levels.

Authors: Joerg Martin Buescher, Wolfram Liebermeister, Matthieu Jules, Markus Uhr, Jan Muntel, Eric Botella, Bernd Hessling, Roelco Jacobus Kleijn, Ludovic Le Chat, François Lecointe, Ulrike Mäder, Pierre Nicolas, Sjouke Piersma, Frank Rügheimer, Dörte Becher, Philippe Bessieres, Elena Bidnenko, Emma L. Denham, Etienne Dervyn, Kevin M. Devine, Geoff Doherty, Samuel Drulhe, Liza Felicori, Mark J. Fogg, Anne Goelzer, Annette Hansen, Colin R. Harwood, Michael Hecker, Sebastian Hubner, Claus Hultschig, Hanne Jarmer, Edda Klipp, Aurélie Leduc, Peter Lewis, Frank Molina, Philippe Noirot, Sabine Peres, Nathalie Pigeonneau, Susanne Pohl, Simon Rasmussen, Bernd Rinn, Marc Schaffer, Julian Schnidder, Benno Schwikowski, Jan Maarten Van Dijl, Patrick Veiga, Sean Walsh, Anthony J. Wilkinson, Jörg Stelling, Stéphane Aymerich, Uwe Sauer

Promoter architecture of mouse olfactory receptor genes [RESEARCH]

Promoter architecture of mouse olfactory receptor genes [RESEARCH]:

Odorous chemicals are detected by the mouse main olfactory epithelium (MOE) by about 1100 types of olfactory receptors (OR) expressed by olfactory sensory neurons (OSNs). Each mature OSN is thought to express only one allele of a single OR gene. Major impediments to understand the transcriptional control of OR gene expression are the lack of a proper characterization of OR transcription start sites (TSSs) and promoters, and of regulatory transcripts at OR loci. We have applied the nanoCAGE technology to profile the transcriptome and the active promoters in the MOE. nanoCAGE analysis revealed the map and architecture of promoters for 87.5% of the mouse OR genes, as well as the expression of many novel noncoding RNAs including antisense transcripts. We identified candidate transcription factors for OR gene expression and among them confirmed by chromatin immunoprecipitation the binding of TBP, EBF1 (OLF1), and MEF2A to OR promoters. Finally, we showed that a short genomic fragment flanking the major TSS of the OR gene Olfr160 (M72) can drive OSN-specific expression in transgenic mice.

Sequence shortening in the rodent ancestor [RESEARCH]

Sequence shortening in the rodent ancestor [RESEARCH]:
Insertions and deletions (indels), together with nucleotide substitutions, are major drivers of sequence evolution. An excess of deletions over insertions in genomic sequences—the so-called deletional bias—has been reported in a wide range of species, including mammals. However, this bias has not been found in the coding sequences of some mammalian species, such as human and mouse. To determine the strength of the deletional bias in mammals, and the influence of mutation and selection, we have quantified indels in both neutrally evolving noncoding sequences and protein-coding sequences, in six mammalian branches: human, macaque, ancestral primate, mouse, rat, and ancestral rodent. The results obtained with an improved algorithm for the placement of insertions in multiple alignments, Prank_+F, indicate that contrary to previous results, the only mammalian branch with a strong deletional bias is the rodent ancestral branch. We estimate that such a bias has resulted in an ~2.5% sequence loss of mammalian syntenic region in the ancestor of the mouse and rat. Further, a comparison of coding and noncoding sequences shows that negative selection is acting more strongly against mutations generating amino acid insertions than against mutations resulting in amino acid deletions. The strength of selection against indels is found to be higher in the rodent branches than in the primate branches, consistent with the larger effective population sizes of the rodents.