scholarly journals A role for YY1 in sex-biased transcription revealed through X-linked promoter activity and allelic binding analyses

2016 ◽  
Author(s):  
Chih-yu Chen ◽  
Wenqiang Shi ◽  
Allison M. Matthews ◽  
Yifeng Li ◽  
David J. Arenillas ◽  
...  
Keyword(s):  
X Chromosome ◽  
Specific Binding ◽  
Positive Association ◽  
Binding Motif ◽  
Transcription Start ◽  
Transcription Factor Binding Motif ◽  
Transcription Start Sites ◽  
Non Coding Rna ◽  
Allelic Gene ◽  
Long Non Coding Rna

AbstractSex differences in susceptibility and progression have been reported in numerous diseases. Female cells have two copies of the X chromosome with X-chromosome inactivation imparting mono-allelic gene silencing for dosage compensation. However, a subset of genes, named escapees, escape silencing and are transcribed bi-allelically resulting in sexual dimorphism. Here we conducted analyses of the sexes using human datasets to gain perspectives in such regulation. We identified transcription start sites of escapees (escTSSs) based on higher transcription levels in female cells using FANTOM5 CAGE data. Significant over-representations of YY1 transcription factor binding motif and ChIP-seq peaks around escTSSs highlighted its positive association with escapees. Furthermore, YY1 occupancy is significantly biased towards the inactive X (Xi) at long non-coding RNA loci that are frequent contacts of Xi-specific superloops. Our study elucidated the importance of YY1 on transcriptional activity on Xi in general through sequence-specific binding, and its involvement at superloop anchors.

scholarly journals Dual regulation of a polyethylene glycol degradative operon by AraC-type and GalR-type regulators in Sphingopyxis macrogoltabida strain 103

Microbiology ◽  
2006 ◽  
Vol 152 (10) ◽  
pp. 3025-3034 ◽  
Author(s):  
Jittima Charoenpanich ◽  
Akio Tani ◽  
Naoko Moriwaki ◽  
Kazuhide Kimbara ◽  
Fusako Kawai
Keyword(s):  
Polyethylene Glycol ◽  
Specific Binding ◽  
Reverse Direction ◽  
Binding Motif ◽  
Transcription Start ◽  
Transcriptional Fusion ◽  
Gene Encoding ◽  
Transcription Start Sites ◽  
Downstream Area ◽  
Promoter Activity Assay

The genes for polyethylene glycol (PEG) catabolism (pegB, C, D, A and E) in Sphingopyxis macrogoltabida strain 103 were shown to form a PEG-inducible operon. The pegR gene, encoding an AraC-type regulator in the downstream area of the operon, is transcribed in the reverse direction. The transcription start sites of the operon were mapped, and three putative σ 70-type promoter sites were identified in the pegB, pegA and pegR promoters. A promoter activity assay showed that the pegB promoter was induced by PEG and oligomeric ethylene glycols, whereas the pegA and pegR promoters were induced by PEG. Deletion analysis of the pegB promoter indicated that the region containing the activator-binding motif of an AraC/XylS-type regulator was required for transcription of the pegBCDAE operon. Gel retardation assays demonstrated the specific binding of PegR to the pegB promoter. Transcriptional fusion studies of pegR with pegA and pegB promoters suggested that PegR regulates the expression of the pegBCDAE operon positively through its binding to the pegB promoter, but PegR does not bind to the pegA promoter. Two specific binding proteins for the pegA promoter were purified and identified as a GalR-type regulator and an H2A histone fragment (histone-like protein, HU). The binding motif of a GalR/LacI-type regulator was found in the pegA and pegR promoters. These results suggested the dual regulation of the pegBCDAE operon through the pegB promoter by an AraC-type regulator, PegR (PEG-independent), and through the pegA and pegR promoters by a GalR/LacI-type regulator together with HU (PEG-dependent).

scholarly journals Association Between Long Non-Coding RNA POLR2E rs3787016 Polymorphism and Cancer Susceptibility: A Meta-analysis of 8725 Cancer Cases and 10710 Controls

2020 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Saeid Ghavami ◽  
Mohsen Taheri ◽  
Mohammad Hashemi
Keyword(s):  
Breast Cancer ◽  
Web Of Science ◽  
Cancer Susceptibility ◽  
Meta Analysis ◽  
Positive Association ◽  
Cancer Development ◽  
Non Coding Rna ◽  
Stratified Analysis ◽  
The Relationship ◽  
Long Non Coding Rna

Objectives: Several studies have reported a correlation between the POLR2E rs3787016 polymorphism and cancer development, but findings are inconsistent. Therefore, we designed the current study to understand how rs3787016 polymorphism impacts cancer susceptibility. Methods: We searched the Scopus, Web of Science, and PubMed databases for studies related to the topic of interest published up to March 2019. A total of 11 relevant studies, encompassing 8,761 cancer cases and 10,534 controls, were retrieved and subject to quantitative analysis. The strength of the relationship was evaluated using the pooled odds ratios (ORs) with 95% confidence intervals (CIs). Results: Overall, the findings proposed a positive association between rs189037 polymorphism and susceptibility to cancer in homozygous (OR = 1.32, 95% CI = 1.11 - 1.57, P = 0.002, TT vs. CC), recessive (OR = 1.21, 95% CI = 1.06-1.39, P = 0.005, TT vs. CT + CC), and allele (OR = 1.12, 95% CI = 1.02-1.22, P = 0.021, T vs. C) genetic models. Stratified analysis showed that rs3787016 increased the risk of prostate and breast cancer. In addition, we found a significant association between the variant and increased cancer risk in Asian and Caucasian populations. Conclusions: In summary, the findings of the current meta-analysis suggest that the POLR2E rs3787016 polymorphism is an indicator of cancer susceptibility.

scholarly journals Targeting the Oncogenic Long Non-coding RNA SLNCR1 by Blocking Its Sequence-Specific Binding to the Androgen Receptor

Cell Reports ◽  
2020 ◽  
Vol 30 (2) ◽  
pp. 541-554.e5 ◽  
Author(s):  
Karyn Schmidt ◽  
Chase A. Weidmann ◽  
Thomas A. Hilimire ◽  
Elaine Yee ◽  
Breanne M. Hatfield ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Specific Binding ◽  
Its Sequence ◽  
Non Coding Rna ◽  
Long Non Coding Rna

scholarly journals GENE-58. ACTIVE TRANSCRIPTION START SITES OF MENINGIOMA SAMPLES ASSOCIATED WITH RISK OF RECURRENCE

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi110-vi110
Author(s):  
Tathiane Malta ◽  
Thais Sarraf Sabedot ◽  
Carlos Carlotti jr ◽  
Houtan Noushmehr
Keyword(s):  
Dna Methylation ◽  
Recurrence Risk ◽  
Transcription Start ◽  
Risk Of Recurrence ◽  
Transcription Start Sites ◽  
Data Alignment ◽  
Non Coding Rna ◽  
Genome Wide ◽  
Substantial Risk ◽  
Active Transcription

Abstract Meningiomas are mostly benign brain tumors but have a substantial risk of recurrence, sometimes to more aggressive subtypes. Recently, a DNA methylation signature in meningioma was described as able to stratify patients by recurrence risk (favorable and unfavorable). It is well recognized that epigenetic deregulation at distinct genomic elements can affect changes in gene expression and contribute to cancer initiation and progression. Our goal for this study is to define genes that are actively expressed or repressed by both DNA methylation and chromatin histone modification (defined by H3K4me3). For this pilot study, we selected two favorable (grades I and II) and two unfavorable (grades II and III) meningioma primary tumor samples (N=4) and mapped H3K4me3 genome-wide and whole-genome DNA methylation, in an attempt to identify active transcription start sites at known promoters. After data alignment, preprocessing and peak calling, we identified 29,514 consensus peaks for H3K4me3. The differential binding analysis resulted in 5,752 H3K4me3 regions that distinguish favorable from unfavorable meningioma, mostly gain of peaks in the unfavorable group. We identified 1,505 peaks overlapping with known promoters, 51% associated with gain of peaks in the unfavorable group. Promoter-associated chromatin changes coincided with hypomethylation in 23 unique genes in the unfavorable group. Genes such as MET, PTEN, and the long non-coding RNA RP11-60L3.1 were identified as potential regulators of meningioma recurrence. Our preliminary results describe the identification of distinct genome-wide changes in chromatin associated with meningioma patient with high risk for recurrence. Identification of candidate genes will provide knowledge of the role of epigenomics in the development of malignant meningioma and of opportunities for targeted therapy.

scholarly journals A RIF1 and KAP1-based, double-bookmarking system generates a toggle switch that stabilises the identities of the active and inactive X chromosomes during random X inactivation in mouse

2020 ◽  
Author(s):  
Elin Enervald ◽  
Rossana Foti ◽  
Lynn Marie Powell ◽  
Agnieszka Piszczek ◽  
Sara C.B. Buonomo
Keyword(s):  
X Chromosome ◽  
Embryonic Stem ◽  
X Inactivation ◽  
Allelic Association ◽  
Toggle Switch ◽  
X Chromosomes ◽  
Non Coding Rna ◽  
The Future ◽  
Long Non Coding Rna ◽  
Stochastic Event

ABSTRACTDosage compensation for the X chromosome-linked genes in female placental mammals is achieved through the random silencing of one of the two X chromosomes. The onset of random X inactivation in mouse embryos and in differentiating embryonic stem cells requires the switch from a symmetric state, where both X chromosomes are equivalent, to an asymmetric state, where the identity of the future inactive and active X chromosomes are assigned. This “choice”, initiated by a stochastic event, needs to evolve into a stable and transmissible state. The transition from bi- to mono-allelic expression of the long non-coding RNA Tsix is thought to be one of the initial events breaking the symmetry of the two X chromosomes. Here we show that the asymmetric expression of Tsix triggers in turn the switch of RIF1 association with the Xist promoter from dynamic and symmetric to stable and asymmetric (on the future inactive X). On the future inactive X, RIF1 then plays an essential role in the upregulation of Xist, thus initiating the consolidation and stable transmission of the identity of the inactive X. Tsix-dependent exclusion of RIF1 from the future active X chromosome in turn permits the association of KAP1 with the Xist promoter, thus marking the future active X chromosome. Timely mono-allelic association of KAP1 is important for a stable choice and for X inactivation. We present here a double-bookmarking system, based on the mutually exclusive relationships of Tsix and RIF1, and RIF1 and KAP1. This system coordinates the identification of the active and inactive X chromosomes and initiates a self-sustaining loop that transforms an initially stochastic event into a stably inherited asymmetric X chromosome state.

scholarly journals Integrative Transcription Start Site Analysis and Physiological Phenotyping Reveal Torpor-specific Expressions in Mouse Skeletal Muscle

2018 ◽  
Author(s):  
Genshiro A Sunagawa ◽  
Ruslan Deviatiiarov ◽  
Kiyomi Ishikawa ◽  
Guzel Gazizova ◽  
Oleg Gusev ◽  
...  
Keyword(s):  
Caloric Intake ◽  
The Body ◽  
Binding Motif ◽  
Transcription Start ◽  
Peripheral Tissues ◽  
Transcription Start Sites ◽  
Site Analysis ◽  
Metabolic States ◽  
Severe Reduction ◽  
Hypometabolic State

SUMMARYMice enter an active hypometabolic state, called daily torpor, when they experience a lowered caloric intake under cool ambient temperature (TA). During torpor, the oxygen consumption rate (VO2) drops to less than 30% of the normal rate without harming the body. This safe but severe reduction in metabolism is attractive for various clinical applications; however, the mechanism and molecules involved are unclear. Therefore, here we systematically analyzed the expression landscape of transcription start sites (TSS) in mouse skeletal muscles under various metabolic states to identify torpor-specific transcription patterns. We analyzed the soleus muscles from 38 mice in torpid, non-torpid, and torpor-deprived conditions, and identified 287 torpor-specific promoters. Furthermore, we found that the transcription factor ATF3 was highly expressed during torpor deprivation and that the ATF3-binding motif was enriched in torpor-specific promoters. Our results demonstrate that the mouse torpor has a distinct hereditary genetic background and its peripheral tissues are useful for studying active hypometabolism.

scholarly journals Contiguous Erosion of the Inactive X in Human Pluripotency Concludes With Global DNA Hypomethylation

2020 ◽  
Author(s):  
Prakhar Bansal ◽  
Stefan F. Pinter
Keyword(s):  
X Chromosome ◽  
Pluripotent Stem Cells ◽  
Regulatory Element ◽  
Chromatin Accessibility ◽  
Integrated Analysis ◽  
Epigenetic Landscape ◽  
Dna Hypomethylation ◽  
Non Coding Rna ◽  
Genome Wide ◽  
Long Non Coding Rna

SUMMARYFemale human pluripotent stem cells (hPSCs) are prone to undergoing X chromosome erosion (XCE), a progressive loss of key epigenetic features on the inactive X that initiates with repression of XIST, the long non-coding RNA required for X inactivation. As a result, previously silenced genes on the eroding X (Xe) reactivate, some of which are thought to provide selective advantages. To-date, the sporadic and progressive nature of XCE has largely obscured its scale, dynamics, and key transition events.To address this knowledge gap, we performed an integrated analysis of DNA methylation (DNAme), chromatin accessibility, and gene expression across hundreds of hPSC samples. Differential methylation across the Xe enables ordering female hPSCs across a trajectory of XCE from initiation to terminal stages. Our results identify a crucial cis-regulatory element for XIST expression, trace contiguously growing domains of reactivation to a few euchromatic origins on the Xi, and indicate that the late-stage Xe impairs DNAme genome-wide. Surprisingly, from this altered epigenetic landscape emerge select features of naïve pluripotency, suggesting its link to X chromosome dosage may be partially conserved in human embryonic development.

scholarly journals Interactions between dosage compensation complex components Msl-1, Msl-2 and NURF component NURF301 with long non-coding RNA gene hsrω

2019 ◽  
Author(s):  
Deo Prakash Chaturvedi
Keyword(s):  
X Chromosome ◽  
Dosage Compensation ◽  
Dosage Compensation Complex ◽  
Chromatin Remodeler ◽  
Down Regulation ◽  
Over Expression ◽  
Non Coding Rna ◽  
Crucial Component ◽  
Male Specific ◽  
Long Non Coding Rna

AbstractHyperactivity of the single X-chromosome in male Drosophila is achieved by establishing a ribonucleoprotein complex, called Dosage Compensation Complex (DCC), on the male X chromosome. Msl-1 and Msl-2 proteins, involved in the initiation and establishing of DCC on male X chromosome, are very crucial component of this complex. In the present study, it has been found here that a long non-coding RNA gene hsrω genetically interacts with Msl-1 as well as Msl-2 and suppresses the lethal phenotype of Msl-1 or Msl-2 down-regulation in its up-regulated background. Additionally, it is also found here that an ATP-dependent chromatin remodeler, NURF301, also interacts with hsrω in same manner. General lethality caused by Act-GAL4 driven global expression of NURF301-RNAi and the male-specific lethality following Msl-1-RNAi or Msl-2-RNAi transgene expression were partially suppressed by over-expression of hsrω, but not by down regulation through hsrω-RNAi. Likewise, eye phenotypes following ey-GAL4 driven down-regulation of NURF301 or Msl-1 or Msl-2 were also partially suppressed by over-expression of hsrω. Act-GAL4 driven global over-expression of hsrω along with Msl-1-RNAi or Msl-2-RNAi transgene substantially restored levels of MSL-2 protein on the male X chromosome. Similarly, levels and distribution of Megator protein, which was reduced and distribution at nuclear rim and in nucleoplasm was affected in the MT and SG nuclei, is also restored when hsrω transcripts are down-regulated in Act-GAL4 driven Msl-1-RNAi or Msl-2-RNAi genetic background. NURF301, a known chromatin remodeler, when down-regulated shows decondensed X chromosome in male larvae. Down-regulation of hsrω results in restoration of chromosome architecture without affecting the level of ISWI protein-another chromatin remodeler protein, known to interacting with hsrω.

scholarly journals Integrative transcription start site analysis and physiological phenotyping reveal torpor-specific expression program in mouse skeletal muscle

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Ruslan Deviatiiarov ◽  
Kiyomi Ishikawa ◽  
Guzel Gazizova ◽  
Takaya Abe ◽  
Hiroshi Kiyonari ◽  
...  
Keyword(s):  
Caloric Intake ◽  
The Body ◽  
Binding Motif ◽  
Transcription Start ◽  
Specific Expression ◽  
Transcription Start Sites ◽  
Site Analysis ◽  
Metabolic States ◽  
Brown Adipose ◽  
Severe Reduction

AbstractMice enter an active hypometabolic state, called daily torpor when they experience a lowered caloric intake under cold ambient temperature. During torpor, the oxygen consumption rate in some animals drops to less than 30% of the normal rate without harming the body. This safe but severe reduction in metabolism is attractive for various clinical applications; however, the mechanism and molecules involved are unclear. Therefore, here we systematically analyzed the gene expression landscape on the level of the RNA transcription start sites in mouse skeletal muscles under various metabolic states to identify torpor-specific transcribed regulatory patterns. We analyzed the soleus muscles from 38 mice in torpid and non-torpid conditions and identified 287 torpor-specific promoters out of 12,862 detected promoters. Furthermore, we found that the transcription factor ATF3 is highly expressed during torpor deprivation and its binding motif is enriched in torpor-specific promoters. Atf3 was also highly expressed in the heart and brown adipose tissue during torpor and systemically knocking out Atf3 affected the torpor phenotype. Our results demonstrate that mouse torpor combined with powerful genetic tools is useful for studying active hypometabolism.

Sign in / Sign up

Export Citation Format

Share Document