Abstract:
:During development of the cerebral cortex, neural stem cells (NSCs) divide symmetrically to proliferate and asymmetrically to generate neurons. Although faithful segregation of mitotic chromosomes is critical for NSC divisions, its fundamental mechanism remains unclear. A class of evolutionarily conserved protein complexes, known as condensins, is thought to be central to chromosome assembly and segregation among eukaryotes. Here we report the first comprehensive genetic study of mammalian condensins, demonstrating that two different types of condensin complexes (condensins I and II) are both essential for NSC divisions and survival in mice. Simultaneous depletion of both condensins leads to severe defects in chromosome assembly and segregation, which in turn cause DNA damage and trigger p53-induced apoptosis. Individual depletions of condensins I and II lead to slower loss of NSCs compared to simultaneous depletion, but they display distinct mitotic defects: chromosome missegregation was observed more prominently in NSCs depleted of condensin II, whereas mitotic delays were detectable only in condensin I-depleted NSCs. Remarkably, NSCs depleted of condensin II display hyperclustering of pericentric heterochromatin and nucleoli, indicating that condensin II, but not condensin I, plays a critical role in establishing interphase nuclear architecture. Intriguingly, these defects are taken over to postmitotic neurons. Our results demonstrate that condensins I and II have overlapping and non-overlapping functions in NSCs, and also provide evolutionary insight into intricate balancing acts of the two condensin complexes.
journal_name
PLoS Genetjournal_title
PLoS geneticsauthors
Nishide K,Hirano Tdoi
10.1371/journal.pgen.1004847subject
Has Abstractpub_date
2014-12-04 00:00:00pages
e1004847issue
12eissn
1553-7390issn
1553-7404pii
PGENETICS-D-14-01812journal_volume
10pub_type
杂志文章相关文献
PLoS Genetics文献大全abstract::Inter-individual variation in gene regulatory elements is hypothesized to play a causative role in adverse drug reactions and reduced drug activity. However, relatively little is known about the location and function of drug-dependent elements. To uncover drug-associated elements in a genome-wide manner, we performed ...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004648
更新日期:2014-10-02 00:00:00
abstract::Neurofibromatosis type 1 is a monogenetic disorder that predisposes individuals to tumor formation and cognitive and behavioral symptoms. The neuronal circuitry and developmental events underlying these neurological symptoms are unknown. To better understand how mutations of the underlying gene (NF1) drive behavioral ...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1008920
更新日期:2020-07-22 00:00:00
abstract::Recent studies of the HapMap lymphoblastoid cell lines have identified large numbers of quantitative trait loci for gene expression (eQTLs). Reanalyzing these data using a novel Bayesian hierarchical model, we were able to create a surprisingly high-resolution map of the typical locations of sites that affect mRNA lev...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000214
更新日期:2008-10-01 00:00:00
abstract::The use of modern molecular biology tools in deciphering the perturbed biochemistry and physiology underlying the obese state has proven invaluable. Identifying the hypothalamic leptin/melanocortin pathway as critical in many cases of monogenic obesity has permitted targeted, hypothesis-driven experiments to be perfor...
journal_title:PLoS genetics
pub_type: 杂志文章,评审
doi:10.1371/journal.pgen.0020188
更新日期:2006-12-29 00:00:00
abstract::Candida albicans is a normal resident of the gastrointestinal tract and also the most prevalent fungal pathogen of humans. It last shared a common ancestor with the model yeast Saccharomyces cerevisiae over 300 million years ago. We describe a collection of 143 genetically matched strains of C. albicans, each of which...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000783
更新日期:2009-12-01 00:00:00
abstract::The antigenic repertoire presented by MHC molecules is generated by the antigen processing and presentation (APP) pathway. We analyzed the evolutionary history of 45 genes involved in APP at the inter- and intra-species level. Results showed that 11 genes evolved adaptively in mammals. Several positively selected site...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004189
更新日期:2014-03-27 00:00:00
abstract::In flowering plants, gene expression in the haploid male gametophyte (pollen) is essential for sperm delivery and double fertilization. Pollen also undergoes dynamic epigenetic regulation of expression from transposable elements (TEs), but how this process interacts with gene expression is not clearly understood. To e...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1008462
更新日期:2020-04-01 00:00:00
abstract::The major transition to eusociality required the evolution of a switch to canalize development into either a reproductive or a helper, the nature of which is currently unknown. Following predictions from the 'theory of facilitated variation', we identify sex differentiation pathways as promising candidates because of ...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1005952
更新日期:2016-03-31 00:00:00
abstract::Mollicutes is a class of parasitic bacteria that have evolved from a common Firmicutes ancestor mostly by massive genome reduction. With genomes under 1 Mbp in size, most Mollicutes species retain the capacity to replicate and grow autonomously. The major goal of this work was to identify the minimal set of proteins t...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004363
更新日期:2014-05-08 00:00:00
abstract::Abnormal accumulation of the microtubule-interacting protein tau is associated with neurodegenerative diseases including Alzheimer's disease (AD). β-amyloid (Aβ) lies upstream of abnormal tau behavior, including detachment from microtubules, phosphorylation at several disease-specific sites, and self-aggregation into ...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1005917
更新日期:2016-03-29 00:00:00
abstract::Exome sequencing has been widely used in detecting pathogenic nonsynonymous single nucleotide variants (SNVs) for human inherited diseases. However, traditional statistical genetics methods are ineffective in analyzing exome sequencing data, due to such facts as the large number of sequenced variants, the presence of ...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004237
更新日期:2014-03-20 00:00:00
abstract::Considerable evidence now supports the idea that the moderate telomere lengthening produced by recombinational telomere elongation (RTE) in a Kluyveromyces lactis telomerase deletion mutant occurs through a roll-and-spread mechanism. However, it is unclear whether this mechanism can account for other forms of RTE that...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1003017
更新日期:2012-01-01 00:00:00
abstract::Plant resistance (R) proteins provide a robust surveillance system to defend against potential pathogens. Despite their importance in plant innate immunity, relatively few of the approximately 170 R proteins in Arabidopsis have well-characterized resistance specificity. In order to identify the R protein responsible f...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000894
更新日期:2010-04-01 00:00:00
abstract::Bromodomain proteins are key regulators of gene expression. How the levels of these factors are regulated in specific environmental conditions is unknown. Previous work has established that expression of yeast Bromodomain factor 2 (BDF2) is limited by spliceosome-mediated decay (SMD). Here we show that BDF2 is subject...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004661
更新日期:2014-09-18 00:00:00
abstract::Progesterone, via the progesterone receptor (PGR), is essential for endometrial stromal cell decidualization, a cellular transformation event in which stromal fibroblasts differentiate into decidual cells. Uterine decidualization supports embryo implantation and placentation as well as subsequent events, which togethe...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1005937
更新日期:2016-04-01 00:00:00
abstract::Both anatomically modern humans and the gastric pathogen Helicobacter pylori originated in Africa, and both species have been associated for at least 100,000 years. Seven geographically distinct H. pylori populations exist, three of which are indigenous to Africa: hpAfrica1, hpAfrica2, and hpNEAfrica. The oldest and m...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1003775
更新日期:2013-01-01 00:00:00
abstract::Evolution of gene regulation is crucial for our understanding of the phenotypic differences between species, populations and individuals. Sequence-specific binding of transcription factors to the regulatory regions on the DNA is a key regulatory mechanism that determines gene expression and hence heritable phenotypic ...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1005639
更新日期:2015-11-06 00:00:00
abstract::Nonreplicating type I uracil auxotrophic mutants of Toxoplasma gondii possess a potent ability to activate therapeutic immunity to established solid tumors by reversing immune suppression in the tumor microenvironment. Here we engineered targeted deletions of parasite secreted effector proteins using a genetically tra...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1006189
更新日期:2016-07-22 00:00:00
abstract::Orofacial clefting is amongst the most common of birth defects, with both genetic and environmental components. Although numerous studies have been undertaken to investigate the complexities of the genetic etiology of this heterogeneous condition, this factor remains incompletely understood. Here, we describe mutation...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1006470
更新日期:2017-01-12 00:00:00
abstract::Chromatin assembly mutants accumulate recombinogenic DNA damage and are sensitive to genotoxic agents. Here we have analyzed why impairment of the H3K56 acetylation-dependent CAF1 and Rtt106 chromatin assembly pathways, which have redundant roles in H3/H4 deposition during DNA replication, leads to genetic instability...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1002376
更新日期:2011-11-01 00:00:00
abstract::The molecular clock of neutral mutations, which represents linear mutation fixation over generations, is theoretically explained by genetic drift in fitness-steady evolution or hitchhiking in adaptive evolution. The present study is the first experimental demonstration for the molecular clock of neutral mutations in a...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1005392
更新日期:2015-07-15 00:00:00
abstract::Disruption of gene regulation by sequence variation in non-coding regions of the genome is now recognised as a significant cause of human disease and disease susceptibility. Sequence variants in cis-regulatory elements (CREs), the primary determinants of spatio-temporal gene regulation, can alter transcription factor ...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1005193
更新日期:2015-06-01 00:00:00
abstract::Polycomb group (PcG) proteins act as evolutionary conserved epigenetic mediators of cell identity because they repress transcriptional programs that are not required at particular developmental stages. Each tissue is likely to have a specific epigenetic profile, which acts as a blueprint for its developmental fate. A ...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1001152
更新日期:2010-10-07 00:00:00
abstract::Cyclophilin B (CyPB), encoded by PPIB, is an ER-resident peptidyl-prolyl cis-trans isomerase (PPIase) that functions independently and as a component of the collagen prolyl 3-hydroxylation complex. CyPB is proposed to be the major PPIase catalyzing the rate-limiting step in collagen folding. Mutations in PPIB cause re...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004465
更新日期:2014-06-26 00:00:00
abstract::In a previous study, we showed that centromere repositioning, that is the shift along the chromosome of the centromeric function without DNA sequence rearrangement, has occurred frequently during the evolution of the genus Equus. In this work, the analysis of the chromosomal distribution of satellite tandem repeats in...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000845
更新日期:2010-02-12 00:00:00
abstract::Phosphoribosyl pyrophosphate synthetase (PRPS) is a rate-limiting enzyme whose function is important for the biosynthesis of purines, pyrimidines, and pyridines. Importantly, while missense mutations of PRPS1 have been identified in neurological disorders such as Arts syndrome, how they contribute to neuropathogenesis...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1008376
更新日期:2019-09-05 00:00:00
abstract::During meiotic prophase I, double-strand breaks (DSBs) initiate homologous recombination leading to non-crossovers (NCOs) and crossovers (COs). In mouse, 10% of DSBs are designated to become COs, primarily through a pathway dependent on the MLH1-MLH3 heterodimer (MutLγ). Mlh3 contains an endonuclease domain that is cr...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1008177
更新日期:2019-06-06 00:00:00
abstract::Most of the genetic architecture of schizophrenia (SCZ) has not yet been identified. Here, we apply a novel statistical algorithm called Covariate-Modulated Mixture Modeling (CM3), which incorporates auxiliary information (heterozygosity, total linkage disequilibrium, genomic annotations, pleiotropy) for each single n...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1005803
更新日期:2016-01-25 00:00:00
abstract::We resequenced and phased 27 kb of DNA within 580 kb of the MHC class II region in 158 population chromosomes, most of which were conserved extended haplotypes (CEHs) of European descent or contained their centromeric fragments. We determined the single nucleotide polymorphism and deletion-insertion polymorphism allel...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004637
更新日期:2014-10-09 00:00:00
abstract::Genetical genomics is a strategy for mapping gene expression variation to expression quantitative trait loci (eQTLs). We performed a genetical genomics experiment in four functionally distinct but developmentally closely related hematopoietic cell populations isolated from the BXD panel of recombinant inbred mouse str...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000692
更新日期:2009-10-01 00:00:00