scholarly journals Transcription factor co-binding patterns drive conserved regulatory outcomes

2017 ◽  
Author(s):  
Adam G. Diehl ◽  
Alan P. Boyle
Keyword(s):  
Transcription Factor ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Regulatory Control ◽  
Regulatory Sequence ◽  
Transcriptional Regulatory ◽  
Genetic Mechanisms ◽  
Transcriptional Regulatory Mechanisms ◽  
Species Specific ◽  
Human And Mouse

ABSTRACTThe mouse has been widely used as a model system in which to study human genetic mechanisms. However, part of the difficulty in translating findings from mouse is that, despite high levels of gene conservation, regulatory control networks between human and mouse have been extensively rewired. To understand common themes of regulatory control we look beyond physical sharing of regulatory sequence, where extensive turnover of individual transcription factor binding sites complicates cross-species prediction of specific functions, and instead look at conserved properties of the regulatory code itself. We define regulatory conservation in terms of a grammar with shared, species-specific, and tissue-specific segments, and show that this grammar is more predictive of shared chromatin states and gene expression profiles than shared occupancy alone. Furthermore, we demonstrate a marked enrichment of disease associated variation in conserved grammatical patterns. These findings offer new understanding of transcriptional regulatory mechanisms shared between human and mouse.

scholarly journals Identifying Transcription Regulatory Elements in the Human and Mouse Genomes Using Tissue-specific Gene Expression Profiles

2007 ◽  
Vol 4 (2) ◽  
pp. 1-23
Author(s):  
Amitava Karmaker ◽  
Kihoon Yoon ◽  
Mark Doderer ◽  
Russell Kruzelock ◽  
Stephen Kwek
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Binding Sites ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Regulatory Elements ◽  
Specific Gene ◽  
Tissue Specific Gene ◽  
Human And Mouse

Summary Revealing the complex interaction between trans- and cis-regulatory elements and identifying these potential binding sites are fundamental problems in understanding gene expression. The progresses in ChIP-chip technology facilitate identifying DNA sequences that are recognized by a specific transcription factor. However, protein-DNA binding is a necessary, but not sufficient, condition for transcription regulation. We need to demonstrate that their gene expression levels are correlated to further confirm regulatory relationship. Here, instead of using a linear correlation coefficient, we used a non-linear function that seems to better capture possible regulatory relationships. By analyzing tissue-specific gene expression profiles of human and mouse, we delineate a list of pairs of transcription factor and gene with highly correlated expression levels, which may have regulatory relationships. Using two closely-related species (human and mouse), we perform comparative genome analysis to cross-validate the quality of our prediction. Our findings are confirmed by matching publicly available TFBS databases (like TRANFAC and ConSite) and by reviewing biological literature. For example, according to our analysis, 80% and 85.71% of the targets genes associated with E2F5 and RELB transcription factors have the corresponding known binding sites. We also substantiated our results on some oncogenes with the biomedical literature. Moreover, we performed further analysis on them and found that BCR and DEK may be regulated by some common transcription factors. Similar results for BTG1, FCGR2B and LCK genes were also reported.

252 DIFFERENCES IN GENE EXPRESSION PROFILES IN MOUSE FERTILIZED BLASTOCYSTS AND DIPLOID BLASTOCYST STAGE PARTHENOTES

2006 ◽  
Vol 18 (2) ◽  
pp. 233
Author(s):  
N.-H. Kim ◽  
S.-K. Cho ◽  
X.-Y. Li ◽  
X.-H. Shen ◽  
X.-S. Cui
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Developmental Process ◽  
Expression Profiles ◽  
Polar Body ◽  
Gene Expression Profiles ◽  
Blastocyst Stage ◽  
Calcium Signal ◽  
Ionophore A23187 ◽  
Parthenogenetic Activation

Following parthenogenetic activation, in the absence of a male contribution, oocytes progress into early gestation. To gain insight into the role of the paternal genome during pre-implantation development, we used microarray to compare gene expression profiles in pre-implantation embryos following fertilization and parthenogenetic activation. Fertilized embryos and oocytes were collected from superovulated C57BL/6J female mice. The oocytes were activated with 50 �M calcium ionophore A23187 for 5 min. After 5 h of culture in M16 medium with 7.5 �g/mL cytochalasin B, oocytes with one polar body and two pronuclei were used in this experiment. The activated oocytes and zygotes were cultured in M16 to the blatocyst stage. Messenger RNA from 50 blastocysts was extracted by means of the Dynabeads mRNA Direct Kit (Dynal, Oslo, Norway), and then linearly amplified for two rounds using the RiboAmp HS RNA Amplification Kit (Arcturus Bioscience, Inc., Mountain View, CA, USA). A set of cRNA targets from the embryos was assembled into a hybridization reaction on the Applied Biosystems 1700 chemiluminescent microarray analyzer (Jung Hwa Scientific Co., Ltd., Seoul, Korea). Each set was repeated three times. All of the correlation coefficients were above 0.9 for experiment replications. Differences in microarray intensities were normalized and grouped by using the Avadis Prophetic 3.3 version, and categories are based on the PANTHER classification system. According to the cDNA microarray data, we additionally categorized genes into transcription- and developmental process-related genes and compared them in both fertilized and parthenogenetically activated blastocysts. Five transcription-related genes (Goosecoid, transcription factor 1, LIM domain, Spi-C transcription factor, and hypoxia inducible factor 3) and seven developmental process related genes (metaxin 1, serine/threonine kinase 22, stromal antigen, butyrophilin, anti-Mullerian hormone type 2 receptor, prolactin-like protein C2, and otoconin 90) were identified in the fertilized blastocysts compared to the blastocyst-stage parthenotes. In contrast, seven transcription- (Amnionless, EHOX-like, calcium signal transducer 2, nuclear receptor 0B, transcription factor CP2, Iroquois related homeobox 3, and zinc finger protein 3) and eight developmental process-related genes (prion protein dublet, X-linked lymphocyte-regulated 3a, muscleblind-like 3, stathmin-like 2, SRY-box-containing gene 7, ephrin B1, muscleblind-like 3, and Iroquois-related homeobox 3) were expressed at a higher level in parthenotes than in fertilized blastocysts. These genes were selected, and their expression levels confirmed, by real-time quantitative RT-PCR. The results indicate that diploid parthenotes at the blastocyst stage may lack or over express genes related to transcription and development processes which possibly result in fetal lethality. Further studies are required to determine whether aberrant gene expression in parthenotes is due to lack of paternal contribution. This work was funded by a grant from the National Research Laboratory Program in Korea.

scholarly journals Transcriptional Repression by the Pho4 Transcription Factor Controls the Timing of SNZ1 Expression

2008 ◽  
Vol 7 (6) ◽  
pp. 949-957 ◽  
Author(s):  
Masafumi Nishizawa ◽  
Tae Komai ◽  
Nobuyuki Morohashi ◽  
Mitsuhiro Shimizu ◽  
Akio Toh-e
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Transcriptional Repression ◽  
Structural Changes ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Nutrient Sensing ◽  
Yeast Cells ◽  
Diauxic Shift

ABSTRACT Nutrient-sensing kinases play important roles for the yeast Saccharomyces cerevisiae to adapt to new nutrient conditions when the nutrient status changes. Our previous global gene expression analysis revealed that the Pho85 kinase, one of the yeast nutrient-sensing kinases, is involved in the changes in gene expression profiles when yeast cells undergo a diauxic shift. We also found that the stationary phase-specific genes SNZ1 and SNO1, whch share a common promoter, are not properly induced when Pho85 is absent. To examine the role of the kinase in SNZ1/SNO1 regulation, we analyzed their expression during the growth of various yeast mutants, including those affecting Pho85 function or lacking the Pho4 transcription factor, an in vivo substrate of Pho85, and tested Pho4 binding by chromatin immunoprecipitation. Pho4 exhibits temporal binding to the SNZ1/SNO1 promoter to down-regulate the promoter activity, and a Δpho4 mutation advances the timing of SNZ1/SNO1 expression. SNZ2, another member of the SNZ/SNO family, is expressed at an earlier growth stage than SNZ1, and Pho4 does not affect this timing, although Pho85 is required for SNZ2 expression. Thus, Pho4 appears to regulate the different timing of the expression of the SNZ/SNO family members. Pho4 binding to the SNZ1/SNO1 promoter is accompanied by alterations in chromatin structure, and Rpd3 histone deacetylase is required for the proper timing of SNZ1/SNO1 expression, while Asf1 histone chaperone is indispensable for their expression. These results imply that Pho4 plays positive and negative roles in transcriptional regulation, with both cases involving structural changes in its target chromatin.

scholarly journals Self-reporting transposons enable simultaneous readout of gene expression and transcription factor binding in single cells

2019 ◽  
Author(s):  
Arnav Moudgil ◽  
Michael N. Wilkinson ◽  
Xuhua Chen ◽  
June He ◽  
Alex J. Cammack ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Single Cell ◽  
Binding Sites ◽  
Expression Profiles ◽  
Single Cells ◽  
Gene Expression Profiles ◽  
Cell Types ◽  
Specific Cell

AbstractIn situ measurements of transcription factor (TF) binding are confounded by cellular heterogeneity and represent averaged profiles in complex tissues. Single cell RNA-seq (scRNA-seq) is capable of resolving different cell types based on gene expression profiles, but no technology exists to directly link specific cell types to the binding pattern of TFs in those cell types. Here, we present self-reporting transposons (SRTs) and their use in single cell calling cards (scCC), a novel assay for simultaneously capturing gene expression profiles and mapping TF binding sites in single cells. First, we show how the genomic locations of SRTs can be recovered from mRNA. Next, we demonstrate that SRTs deposited by the piggyBac transposase can be used to map the genome-wide localization of the TFs SP1, through a direct fusion of the two proteins, and BRD4, through its native affinity for piggyBac. We then present the scCC method, which maps SRTs from scRNA-seq libraries, thus enabling concomitant identification of cell types and TF binding sites in those same cells. As a proof-of-concept, we show recovery of cell type-specific BRD4 and SP1 binding sites from cultured cells. Finally, we map Brd4 binding sites in the mouse cortex at single cell resolution, thus establishing a new technique for studying TF biology in situ.

scholarly journals Identification of novel genes including rpmF and yjjQ critical for Type II persister formation in Escherichia coli

2018 ◽  
Author(s):  
Shuang Liu ◽  
Nan Wu ◽  
Shanshan Zhang ◽  
Yumeng Zhang ◽  
Wenhong Zhang ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Expression Profiles ◽  
Ribosomal Subunit ◽  
Critical Time ◽  
Gene Expression Profiles ◽  
Novel Genes ◽  
E Coli ◽  
Persistent Infections ◽  
Bona Fide ◽  
Emergence Phase

AbstractPersister cells, which are characterized by inactive metabolism and tolerance to antibiotics or stresses, pose a significant challenge to the treatment of many persistent infections. Although multiple genes have been reported to be involved in persister formation through transposon mutant library screens, how persisters are formed during the natural process of persister formation as the culture transitions from log phase to stationary phase is unclear. Here, using E. coli as a model, we performed a comprehensive transcriptome analysis of gene expression profiles of successive cultures of an E. coli culture at different critical time points, starting from persister-free S1-nonexistence phase (3h) to persister appearing S2-emergence phase (4h), and persister abundant stage S3-abundance phase (5h). The differentially expressed genes (≥2-fold) in persister appearing stage (S1 to S2 transition) and persister abundant stage (S1 to S3) were compared, and 51 and 29 genes were identified to be up-regulated, respectively. Importantly, 13 genes (gnsA, gnsB, ybfA, yjjQ, ymdF, yhdU, csgD, yncN, rpmF, ydcX, yohJ, ssrA, rbsD) overlap in both persister S2-emergence phase and S3-abundance phase, including a member of the trans-translation pathway (ssrA) as well as an orphan toxin (ydcX), which are two well-known persister genes while the remaining 11 novel genes (gnsA, gnsB, ybfA, yjjQ, ymdF, yhdU, csgD, yncN, rpmF, yohJ, rbsD) have not been reported previously. Persister levels of 7 constructed knockout mutants (ΔgnsA, ΔybfA, ΔyjjQ, ΔyhdU, ΔcsgD, ΔyohJ and ΔrpmF) and 10 overexpression strains (gnsA, gnsB, ybfA, yjjQ, ymdF, yhdU, csgD, rpmF, yohJ, rbsD) in E. coli uropathogenic strain UTI89 were determined upon treatment with different cidal antibiotics (ampicillin, levofloxacin and gentamicin). Additionally, ranking of these overlapping genes according to their impact on persister levels were also performed. Two genes (rpmF encoding 50S ribosomal subunit protein L32, and yjjQ encoding a putative LuxR-type transcription factor) showed the most obvious phenotype on persister levels in both knockout and overexpression studies, which suggests they are broad and key factors for persister formation. While previous studies cannot distinguish if a given persister gene is involved in persister formation or persister survival, our findings clearly identify novel persister forming genes and pathways involving a ribosome protein and a LuxR type transcription factor during the bona fide persister formation process and may have implications for developing improved treatment of persistent infections.

scholarly journals Post-transcriptional mechanisms distinguish human and chimp forebrain progenitor cells

2019 ◽  
Author(s):  
Daniela A Grassi ◽  
Per Ludvik Brattås ◽  
Jeovanis G Valdés ◽  
Melinda Rezeli ◽  
Marie E Jönsson ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Transcriptional Control ◽  
Neural Progenitor Cells ◽  
Specific Expression ◽  
Control Of Gene Expression ◽  
Transcriptional Regulatory ◽  
Transcriptional Regulatory Mechanisms ◽  
Species Specific ◽  
High Level ◽  
Rna Levels

AbstractThe forebrain has expanded in size and complexity during hominoid evolution. The contribution of post-transcriptional control of gene expression to this process is unclear. Using in-depth proteomics in combination with bulk and single-cell RNA sequencing, we analyzed protein and RNA levels of almost 5,000 genes in human and chimpanzee forebrain neural progenitor cells. We found that species differences in protein expression level was often independent of RNA levels, and more frequent than transcriptomic differences. Low-abundant proteins were more likely to show species-specific expression levels, while proteins expressed at a high level appeared to have evolved under stricter constraints. Our study implicates a previously unappreciated broad and important role for post-transcriptional regulatory mechanisms in the evolution of the human forebrain.

scholarly journals Transcriptional dysregulation study reveals a core network involving the genesis for Alzheimer’s disease

2017 ◽  
Author(s):  
Guofeng Meng ◽  
Hongkang Mei
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Synaptic Function ◽  
Core Network ◽  
Disease Etiology ◽  
Transcriptional Dysregulation ◽  
Disease States ◽  
Human And Mouse

AbstractBackgroundThe pathogenesis of Alzheimer’s disease is associated with dysregulation at different levels from transcriptome to cellular functioning. Such complexity necessitates investigations of disease etiology to be carried out considering multiple aspects of the disease and the use of independent strategies. The established works more emphasized on the structural organization of gene regulatory network while neglecting the internal regulation changes.MethodsApplying a strategy different from popularly used co-expression network analysis, this study investigated the transcriptional dysregulations during the transition from normal to disease states.Results97 genes were predicted as dysregulated genes, which were also associated with clinical outcomes of Alzheimer’s disease. Both the co-expression and differential co-expression analysis suggested these genes to be interconnected as a core network and that their regulations were strengthened during the transition to disease states. Functional studies suggested the dysregulated genes to be associated with aging and synaptic function. Further, we checked the evolutionary conservation of the gene co-expression and found that human and mouse brain might have divergent transcriptional co-regulation even when they had conserved gene expression profiles.ConclusionOverall, our study reveals a profile of transcriptional dysregulation in the genesis of Alzheimer’s disease by forming a core network with altered regulation; the core network is associated with Alzheimer’s diseases by affecting the aging and synaptic functions related genes; the gene regulation in brain may not be conservative between human and mouse.

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