scholarly journals Hoxa1 and TALE proteins display cross-regulatory interactions and form a combinatorial binding code on Hoxa1 targets

2016 ◽  
Author(s):  
Bony De Kumar ◽  
Hugo J. Parker ◽  
Ariel Paulson ◽  
Mark E. Parrish ◽  
Irina Pushel ◽  
...  
Keyword(s):  
Es Cells ◽  
Hox Proteins ◽  
Binding Motifs ◽  
Functional Roles ◽  
Regulatory Interactions ◽  
Mouse Es Cells ◽  
Genome Wide ◽  
A Genome ◽  
Combinatorial Interactions ◽  
Insight Into

AbstractHoxa1 has diverse functional roles in differentiation and development. We have identified and characterized properties of regions bound by Hoxa1 on a genome-wide basis in differentiating mouse ES cells. Hoxa1 bound regions are enriched for clusters of consensus binding motifs for Hox, Pbx and Meis and many display co-occupancy of Pbx and Meis. Pbx and Meis are members of the TALE family and genome-wide analysis of multiple TALE members (Pbx, Meis, TGIF, Prep1 and Prep2) show that nearly all Hoxa1 targets display occupancy of one or more TALE members. The combinatorial binding patterns of TALE proteins defines distinct classes of Hoxa1 targets and indicates a role as cofactors in modulating the specificity of Hox proteins. We also discovered extensive auto- and cross-regulatory interactions among the Hoxa1 and TALE genes. This study provides new insight into a regulatory network involving combinatorial interactions between Hoxa1 and TALE proteins.

scholarly journals A genome-wide knock-out screen for actors of epigenetic silencing reveals new regulators of germline genes and 2-cell like cell state

2021 ◽  
Author(s):  
Nikhil Gupta ◽  
Lounis Yakhou ◽  
Julien Richard Albert ◽  
Fumihito Miura ◽  
Laure Ferry ◽  
...  
Keyword(s):  
Es Cells ◽  
Epigenetic Mechanisms ◽  
Mammalian Development ◽  
Reporter System ◽  
Transcriptional Responses ◽  
Knock Out ◽  
Mouse Es Cells ◽  
Genome Wide ◽  
A Genome ◽  
Germline Genes

Epigenetic mechanisms are essential to establish and safeguard cellular identities in mammals. They dynamically regulate the expression of genes, transposable elements, and higher-order chromatin structures. Expectedly, these chromatin marks are indispensable for mammalian development and alterations often lead to diseases such as cancer. Molecularly, epigenetic mechanisms rely on factors to establish patterns, interpret them into a transcriptional output, and maintain them across cell divisions. A global picture of these phenomena has started to emerge over the years, yet many of the molecular actors remain to be discovered. In this context, we have developed a reporter system sensitive to epigenetic perturbations to report on repressive pathways based on Dazl, which is normally repressed in mouse ES cells. We used this system for a genome-wide CRISPR knock-out screen, which yielded expected hits (DNMT1, UHRF1, MGA), as well as novel candidates. We prioritized the candidates by secondary screens, and led further experiments on 6 of them: ZBTB14, KDM5C, SPOP, MCM3AP, BEND3, and KMT2D. Our results show that all 6 candidates regulate the expression of germline genes. In addition, we find that removal of ZBTB14, KDM5C, SPOP and MCM3AP led to similar transcriptional responses, including a reactivation of the 2-cell like cell (2CLC) signature. Therefore, our genetic screen has identified new regulators of key cellular states.

scholarly journals Molecular cloning of RBCS genes in Selaginella and the evolution of the rbcS gene family

2015 ◽  
Vol 67 (2) ◽  
pp. 373-383
Author(s):  
Bo Wang ◽  
Su Yingjuan ◽  
Ting Wang
Keyword(s):  
Gene Family ◽  
Physcomitrella Patens ◽  
Higher Plants ◽  
Genome Wide ◽  
A Genome ◽  
Rbcs Gene ◽  
Rbcs Genes ◽  
Selaginella Moellendorffii ◽  
Insight Into ◽  
Major Domain

Rubisco small subunits (RBCS) are encoded by a nuclear rbcS multigene family in higher plants and green algae. However, owing to the lack of rbcS sequences in lycophytes, the characteristics of rbcS genes in lycophytes is unclear. Recently, the complete genome sequence of the lycophyte Selaginella moellendorffii provided the first insight into the rbcS gene family in lycophytes. To understand further the characteristics of rbcS genes in other Selaginella, the full length of rbcS genes (rbcS1 and rbcS2) from two other Selaginella species were isolated. Both rbcS1 and rbcS2 genes shared more than 97% identity among three Selaginella species. RBCS proteins from Selaginella contained the Pfam RBCS domain F00101, which was a major domain of other plant RBCS proteins. To explore the evolution of the rbcS gene family across Selaginella and other plants, we identified and performed comparative analysis of the rbcS gene family among 16 model plants based on a genome-wide analysis. The results showed that (i) two rbcS genes were obtained in Selaginella, which is the second fewest number of rbcS genes among the 16 representative plants; (ii) an expansion of rbcS genes occurred in the moss Physcomitrella patens; (iii) only RBCS proteins from angiosperms contained the Pfam PF12338 domains, and (iv) a pattern of concerted evolution existed in the rbcS gene family. Our study provides new insights into the evolution of the rbcS gene family in Selaginella and other plants.

scholarly journals A Comprehensive Survey on the Terpene Synthase Gene Family Provides New Insight into Its Evolutionary Patterns

2019 ◽  
Vol 11 (8) ◽  
pp. 2078-2098 ◽  
Author(s):  
Shu-Ye Jiang ◽  
Jingjing Jin ◽  
Rajani Sarojam ◽  
Srinivasan Ramachandran
Keyword(s):  
Gene Family ◽  
Large Scale ◽  
Family Members ◽  
Terpene Synthase ◽  
Limited Information ◽  
Terpene Synthases ◽  
Genome Wide ◽  
A Genome ◽  
Family Expansion ◽  
Insight Into

Abstract Terpenes are organic compounds and play important roles in plant growth and development as well as in mediating interactions of plants with the environment. Terpene synthases (TPSs) are the key enzymes responsible for the biosynthesis of terpenes. Although some species were employed for the genome-wide identification and characterization of the TPS family, limited information is available regarding the evolution, expansion, and retention mechanisms occurring in this gene family. We performed a genome-wide identification of the TPS family members in 50 sequenced genomes. Additionally, we also characterized the TPS family from aromatic spearmint and basil plants using RNA-Seq data. No TPSs were identified in algae genomes but the remaining plant species encoded various numbers of the family members ranging from 2 to 79 full-length TPSs. Some species showed lineage-specific expansion of certain subfamilies, which might have contributed toward species or ecotype divergence or environmental adaptation. A large-scale family expansion was observed mainly in dicot and monocot plants, which was accompanied by frequent domain loss. Both tandem and segmental duplication significantly contributed toward family expansion and expression divergence and played important roles in the survival of these expanded genes. Our data provide new insight into the TPS family expansion and evolution and suggest that TPSs might have originated from isoprenyl diphosphate synthase genes.

scholarly journals Admixture into and within sub-Saharan Africa

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
George BJ Busby ◽  
Gavin Band ◽  
Quang Si Le ◽  
Muminatou Jallow ◽  
Edith Bougama ◽  
...  
Keyword(s):  
Gene Flow ◽  
Geographic Region ◽  
Sub Saharan Africa ◽  
Genome Wide ◽  
A Genome ◽  
Depth Analysis ◽  
Shared Ancestry ◽  
Sub Saharan ◽  
Linguistic Groups ◽  
Insight Into

Similarity between two individuals in the combination of genetic markers along their chromosomes indicates shared ancestry and can be used to identify historical connections between different population groups due to admixture. We use a genome-wide, haplotype-based, analysis to characterise the structure of genetic diversity and gene-flow in a collection of 48 sub-Saharan African groups. We show that coastal populations experienced an influx of Eurasian haplotypes over the last 7000 years, and that Eastern and Southern Niger-Congo speaking groups share ancestry with Central West Africans as a result of recent population expansions. In fact, most sub-Saharan populations share ancestry with groups from outside of their current geographic region as a result of gene-flow within the last 4000 years. Our in-depth analysis provides insight into haplotype sharing across different ethno-linguistic groups and the recent movement of alleles into new environments, both of which are relevant to studies of genetic epidemiology.

scholarly journals TERRA regulate the transcriptional landscape of pluripotent cells through TRF1-dependent recruitment of PRC2

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Rosa María Marión ◽  
Juan J Montero ◽  
Isabel López de Silanes ◽  
Osvaldo Graña-Castro ◽  
Paula Martínez ◽  
...  
Keyword(s):  
Cell Fate ◽  
Es Cells ◽  
Epigenetic Changes ◽  
Pluripotent Cells ◽  
Telomere Repeat ◽  
Mouse Es Cells ◽  
Genome Wide ◽  
Binding Factor ◽  
Transcriptional Landscape ◽  
Pluripotency Genes

The mechanisms that regulate pluripotency are still largely unknown. Here, we show that Telomere Repeat Binding Factor 1 (TRF1), a component of the shelterin complex, regulates the genome-wide binding of polycomb and polycomb H3K27me3 repressive marks to pluripotency genes, thereby exerting vast epigenetic changes that contribute to the maintenance of mouse ES cells in a naïve state. We further show that TRF1 mediates these effects by regulating TERRA, the lncRNAs transcribed from telomeres. We find that TERRAs are enriched at polycomb and stem cell genes in pluripotent cells and that TRF1 abrogation results in increased TERRA levels and in higher TERRA binding to those genes, coincidental with the induction of cell-fate programs and the loss of the naïve state. These results are consistent with a model in which TRF1-dependent changes in TERRA levels modulate polycomb recruitment to pluripotency and differentiation genes. These unprecedented findings explain why TRF1 is essential for the induction and maintenance of pluripotency.

scholarly journals DETECTION OF SELECTION SIGNALS IN CATTLE POPULATIONS BY PCA

AGROFOR ◽  
2020 ◽  
Vol 5 (2) ◽  
Author(s):  
Barbora OLŠANSKÁ ◽  
Radovan KASARDA ◽  
Kristína LEHOCKÁ ◽  
Nina MORAVČÍKOVÁ
Keyword(s):  
Muscle Development ◽  
Principal Component ◽  
Coat Colour ◽  
Genome Wide ◽  
A Genome ◽  
Somatic Diversification ◽  
Close Genetic Relationship ◽  
Insight Into ◽  
Selection Of ◽  
Genome Wide Scan

The presented study provides a genome-wide scan of selection signals in cattle by principal component analysis (PCA). The aim was to identify SNP affected by intensive selection based on package PCAdapt implemented under software R. This analysis provided insight into the association between the SNP frequencies related to population differentiation. The four cattle populations were involved in the analysis (Slovak Spotted cattle, Ayrshire, Swiss Simmental and Holstein) with overall 272 of genotyped individuals. After applying quality control, the final dataset consisted of 35 675 SNPs, with an overall length of 2496.14 Mb and average space between adjacent SNP 70.03 ± 76.1 kb. After performing PCA analysis, the uniqueness of the breeds was revealed. On the other hand, a close genetic relationship and eleven SNPs affected by selection were found, with a position close to 162 genes involved in the various biological processes. The majority of genes were involved in the positive regulation of adenylate cyclase activity, embryo development and somatic diversification of immune receptors via somatic mutation. Several candidate genes for genetic control of the immune system (DNAJB9), muscle development (SEPT7, TRIM32, ROCK1, NRAP, PZDZ8, HSPA12A and FGFR2), milk production (SOCS5, CD46), reproduction (LHCGR, EEPD1, FSHR) and coat colour (KIT) were identified. Our results provide insights into the regions of the genome affected by the intensive selection of analysed cattle populations.

scholarly journals SLC19A1 is an importer of the immunotransmitter cGAMP

2019 ◽  
Author(s):  
Anthony F. Cordova ◽  
Christopher Ritchie ◽  
Gaelen T. Hess ◽  
Michael C. Bassik ◽  
Lingyin Li
Keyword(s):  
Immune Response ◽  
Clinical Trials ◽  
Cell Membrane ◽  
Cancer Therapeutics ◽  
Host Cells ◽  
Genome Wide ◽  
A Genome ◽  
Crispr Screen ◽  
Sting Pathway ◽  
Insight Into

Abstract2’3’-cyclic-GMP-AMP (cGAMP) is a second messenger that activates the antiviral Stimulator of Interferon Genes (STING) pathway. We recently identified a novel role for cGAMP as a soluble, extracellular immunotransmitter that is produced and secreted by cancer cells. Secreted cGAMP is then sensed by host cells, eliciting an antitumoral immune response. Due to the antitumoral effects of cGAMP, other CDN-based STING agonists are currently under investigation in clinical trials for metastatic solid tumors. However, it is unknown how cGAMP and other CDNs cross the cell membrane to activate intracellular STING. Using a genome-wide CRISPR screen we identified SLC19A1 as the first known importer of cGAMP and other CDNs, including the investigational new drug 2′3′-bisphosphosphothioate-cyclic-di-AMP (2′3′-CDAS). These discoveries will provide insight into cGAMP’s role as an immunotransmitter and aid in the development of more targeted CDN-based cancer therapeutics.

scholarly journals Genome-wide synthetic lethal CRISPR screen identifies FIS1 as a genetic interactor of ALS-linked C9ORF72

2019 ◽  
Author(s):  
Noori Chai ◽  
Michael S. Haney ◽  
Julien Couthouis ◽  
David W. Morgens ◽  
Alyssa Benjamin ◽  
...  
Keyword(s):  
Genetic Interaction ◽  
Mitochondrial Fission ◽  
Loss Of Function ◽  
Synthetic Lethal ◽  
Genome Wide ◽  
A Genome ◽  
Crispr Screen ◽  
Insight Into ◽  
Mitochondrial Membrane Protein ◽  
Lateral Sclerosis

AbstractMutations in the C9ORF72 gene are the most common cause of amyotrophic lateral sclerosis (ALS). Both toxic gain of function and loss of function pathogenic mechanisms have been proposed. Accruing evidence from mouse knockout studies point to a role for C9ORF72 as a regulator of immune function. To provide further insight into its cellular function, we performed a genome-wide synthetic lethal CRISPR screen in human myeloid cells lacking C9ORF72. We discovered a strong synthetic lethal genetic interaction between C9ORF72 and FIS1, which encodes a mitochondrial membrane protein involved in mitochondrial fission and mitophagy. Mass spectrometry experiments revealed that in C9ORF72 knockout cells, FIS1 strongly bound to a class of immune regulators that activate the receptor for advanced glycation end (RAGE) products and trigger inflammatory cascades. These findings present a novel genetic interactor for C9ORF72 and suggest a compensatory role for FIS1 in suppressing inflammatory signaling in the absence of C9ORF72.

scholarly journals Comparison of the Microsatellite Distribution Patterns in the Genomes of Euarchontoglires at the Taxonomic Level

2021 ◽  
Vol 12 ◽  
Author(s):  
Xuhao Song ◽  
Tingbang Yang ◽  
Xinyi Zhang ◽  
Ying Yuan ◽  
Xianghui Yan ◽  
...  
Keyword(s):  
Genome Size ◽  
Gc Content ◽  
Distribution Patterns ◽  
Functional Roles ◽  
Tree Shrews ◽  
Copy Numbers ◽  
Genome Wide ◽  
A Genome ◽  
Dinucleotide Motif ◽  
Evolution Of Mammals

Microsatellite or simple sequence repeat (SSR) instability within genes can induce genetic variation. The SSR signatures remain largely unknown in different clades within Euarchontoglires, one of the most successful mammalian radiations. Here, we conducted a genome-wide characterization of microsatellite distribution patterns at different taxonomic levels in 153 Euarchontoglires genomes. Our results showed that the abundance and density of the SSRs were significantly positively correlated with primate genome size, but no significant relationship with the genome size of rodents was found. Furthermore, a higher level of complexity for perfect SSR (P-SSR) attributes was observed in rodents than in primates. The most frequent type of P-SSR was the mononucleotide P-SSR in the genomes of primates, tree shrews, and colugos, while mononucleotide or dinucleotide motif types were dominant in the genomes of rodents and lagomorphs. Furthermore, (A)n was the most abundant motif in primate genomes, but (A)n, (AC)n, or (AG)n was the most abundant motif in rodent genomes which even varied within the same genus. The GC content and the repeat copy numbers of P-SSRs varied in different species when compared at different taxonomic levels, reflecting underlying differences in SSR mutation processes. Notably, the CDSs containing P-SSRs were categorized by functions and pathways using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes annotations, highlighting their roles in transcription regulation. Generally, this work will aid future studies of the functional roles of the taxonomic features of microsatellites during the evolution of mammals in Euarchontoglires.

scholarly journals Tracking the embryonic stem cell transition from ground state pluripotency

2016 ◽  
Author(s):  
Tüzer Kalkan ◽  
Nelly Olova ◽  
Mila Roode ◽  
Carla Mulas ◽  
Heather J. Lee ◽  
...  
Keyword(s):  
Ground State ◽  
Es Cells ◽  
Single Cells ◽  
Embryonic Stem ◽  
List Type ◽  
Es Cell ◽  
Genome Wide ◽  
Developmental Progression ◽  
A Genome ◽  
Lineage Priming

SummaryMouse embryonic stem (ES) cells are locked into self-renewal by shielding from inductive cues. Release from this ground state in minimal conditions offers a system for delineating developmental progression from naive pluripotency. Here we examined the initial transition of ES cells. The population behaves asynchronously. We therefore exploited a short-half-life Rex1::GFP reporter to isolate cells either side of exit from naive status. Extinction of ES cell identity in single cells is acute. It occurs only after near-complete elimination of naïve pluripotency factors, but precedes appearance of lineage specification markers. Cells newly departed from the ES cell state exhibit global transcriptome features consistent with features of early post-implantation epiblast and distinct from primed epiblast. They also exhibit a genome-wide increase in DNA methylation, intermediate between early and late epiblast. These findings are consistent with the proposition that naïve cells transition to a discrete formative phase of pluripotency preparatory to lineage priming.HighlightsThe Rex1 destabilized GFP reporter demarcates naive pluripotency.Exit from the naive state is asynchronous in the population.Transition is relatively acute in individual cells and precedes lineage priming.Transcriptome and DNA methylome reflect events in the pre-gastrulation embryo.

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