scholarly journals M1BP cooperates with CP190 to activate transcription at TAD borders and promote chromatin insulator activity

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Indira Bag ◽  
Shue Chen ◽  
Leah F. Rosin ◽  
Yang Chen ◽  
Chen-Yu Liu ◽  
...  
Keyword(s):  
Genome Organization ◽  
Chromatin Accessibility ◽  
Chromatin Binding ◽  
Core Complex ◽  
Chromatin Insulator ◽  
Genome Wide ◽  
Transcription Factor Motif ◽  
Insulator Activity ◽  
The Relationship ◽  
Transcriptional State

AbstractGenome organization is driven by forces affecting transcriptional state, but the relationship between transcription and genome architecture remains unclear. Here, we identified the Drosophila transcription factor Motif 1 Binding Protein (M1BP) in physical association with the gypsy chromatin insulator core complex, including the universal insulator protein CP190. M1BP is required for enhancer-blocking and barrier activities of the gypsy insulator as well as its proper nuclear localization. Genome-wide, M1BP specifically colocalizes with CP190 at Motif 1-containing promoters, which are enriched at topologically associating domain (TAD) borders. M1BP facilitates CP190 chromatin binding at many shared sites and vice versa. Both factors promote Motif 1-dependent gene expression and transcription near TAD borders genome-wide. Finally, loss of M1BP reduces chromatin accessibility and increases both inter- and intra-TAD local genome compaction. Our results reveal physical and functional interaction between CP190 and M1BP to activate transcription at TAD borders and mediate chromatin insulator-dependent genome organization.

scholarly journals M1BP cooperates with CP190 to activate transcription at TAD borders and promote chromatin insulator activity

2020 ◽  
Author(s):  
Indira Bag ◽  
Shue Chen ◽  
Leah F. Rosin ◽  
Yang Chen ◽  
Chen-Yu Liu ◽  
...  
Keyword(s):  
Genome Organization ◽  
Chromatin Binding ◽  
Core Complex ◽  
Chromatin Insulator ◽  
Genome Wide ◽  
Transcription Factor Motif ◽  
Insulator Activity ◽  
Enhancer Blocking ◽  
The Relationship ◽  
Transcriptional State

ABSTRACTGenome organization is driven by forces affecting transcriptional state, but the relationship between transcription and genome architecture remains unclear. Here, we identified the Drosophila transcription factor Motif 1 Binding Protein (M1BP) in physical association with the gypsy chromatin insulator core complex, including the universal insulator protein CP190. M1BP is required for enhancer-blocking and barrier activities of the gypsy insulator as well as its proper nuclear localization. Genome-wide, M1BP specifically colocalizes with CP190 at Motif 1-containing promoters, which are enriched at topologically associating domain (TAD) borders. M1BP is required for CP190 chromatin binding at many shared sites, and CP190 also affects M1BP chromatin association. Both factors are required for Motif 1-dependent gene expression and transcription near TAD borders genome-wide. Finally, loss of M1BP alters local genome compaction. Our results reveal physical and functional interaction between CP190 and M1BP to activate transcription at TAD borders and mediate chromatin insulator-dependent genome organization.

scholarly journals DNA methylation-linked chromatin accessibility affects genomic architecture in Arabidopsis

2021 ◽  
Vol 118 (5) ◽  
pp. e2023347118
Author(s):  
Zhenhui Zhong ◽  
Suhua Feng ◽  
Sascha H. Duttke ◽  
Magdalena E. Potok ◽  
Yiwei Zhang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Genome Organization ◽  
Epigenetic Modification ◽  
Chromatin Accessibility ◽  
Biological Processes ◽  
Profound Impact ◽  
Chromatin Interactions ◽  
Genomic Architecture ◽  
Genome Wide ◽  
Different Types

DNA methylation is a major epigenetic modification found across species and has a profound impact on many biological processes. However, its influence on chromatin accessibility and higher-order genome organization remains unclear, particularly in plants. Here, we present genome-wide chromatin accessibility profiles of 18 Arabidopsis mutants that are deficient in CG, CHG, or CHH DNA methylation. We find that DNA methylation in all three sequence contexts impacts chromatin accessibility in heterochromatin. Many chromatin regions maintain inaccessibility when DNA methylation is lost in only one or two sequence contexts, and signatures of accessibility are particularly affected when DNA methylation is reduced in all contexts, suggesting an interplay between different types of DNA methylation. In addition, we found that increased chromatin accessibility was not always accompanied by increased transcription, suggesting that DNA methylation can directly impact chromatin structure by other mechanisms. We also observed that an increase in chromatin accessibility was accompanied by enhanced long-range chromatin interactions. Together, these results provide a valuable resource for chromatin architecture and DNA methylation analyses and uncover a pivotal role for methylation in the maintenance of heterochromatin inaccessibility.

scholarly journals Integrating transcription factor abundance with chromatin accessibility in human erythroid lineage commitment

2021 ◽  
Author(s):  
Reema Baskar ◽  
Amy F Chen ◽  
Patricia M.B. Favaro ◽  
Warren Reynolds ◽  
Fabian Muller ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Chromatin Accessibility ◽  
Erythroid Cell ◽  
Open Chromatin ◽  
Protein Abundance ◽  
Intracellular Protein ◽  
Simultaneous Quantification ◽  
Genome Wide ◽  
Transcription Factor Motif ◽  
Factor Abundance

We present InTAC-seq, a method for simultaneous quantification of genome-wide open chromatin and intracellular protein abundance in fixed cells. Using InTAC we directly observe variation in chromatin accessibility and transcription factor motif occupancy driven by differences in transcription factor protein abundance. By purifying bone marrow progenitor cells based on GATA1 protein expression, we establish its role in both functional and epigenetic restriction of erythroid cell identity in human hematopoiesis.

Migraine: Genetic Variants and Clinical Phenotypes

2019 ◽  
Vol 26 (34) ◽  
pp. 6207-6221 ◽  
Author(s):  
Innocenzo Rainero ◽  
Alessandro Vacca ◽  
Flora Govone ◽  
Annalisa Gai ◽  
Lorenzo Pinessi ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Association Studies ◽  
Mthfr Gene ◽  
Genome Wide Association Studies ◽  
Clinical Phenotypes ◽  
Network Analyses ◽  
Genome Wide ◽  
Genomic Studies ◽  
The Common ◽  
The Relationship

Migraine is a common, chronic neurovascular disorder caused by a complex interaction between genetic and environmental risk factors. In the last two decades, molecular genetics of migraine have been intensively investigated. In a few cases, migraine is transmitted as a monogenic disorder, and the disease phenotype cosegregates with mutations in different genes like CACNA1A, ATP1A2, SCN1A, KCNK18, and NOTCH3. In the common forms of migraine, candidate genes as well as genome-wide association studies have shown that a large number of genetic variants may increase the risk of developing migraine. At present, few studies investigated the genotype-phenotype correlation in patients with migraine. The purpose of this review was to discuss recent studies investigating the relationship between different genetic variants and the clinical characteristics of migraine. Analysis of genotype-phenotype correlations in migraineurs is complicated by several confounding factors and, to date, only polymorphisms of the MTHFR gene have been shown to have an effect on migraine phenotype. Additional genomic studies and network analyses are needed to clarify the complex pathways underlying migraine and its clinical phenotypes.

scholarly journals High-throughput single-cell chromatin accessibility CRISPR screens enable unbiased identification of regulatory networks in cancer

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Sarah E. Pierce ◽  
Jeffrey M. Granja ◽  
William J. Greenleaf
Keyword(s):  
Transcription Factor ◽  
Single Cell ◽  
Cancer Cells ◽  
High Throughput ◽  
Regulatory Networks ◽  
Temporal Dynamics ◽  
Chromatin Accessibility ◽  
Regulatory Regions ◽  
Factor Binding ◽  
Genome Wide

AbstractChromatin accessibility profiling can identify putative regulatory regions genome wide; however, pooled single-cell methods for assessing the effects of regulatory perturbations on accessibility are limited. Here, we report a modified droplet-based single-cell ATAC-seq protocol for perturbing and evaluating dynamic single-cell epigenetic states. This method (Spear-ATAC) enables simultaneous read-out of chromatin accessibility profiles and integrated sgRNA spacer sequences from thousands of individual cells at once. Spear-ATAC profiling of 104,592 cells representing 414 sgRNA knock-down populations reveals the temporal dynamics of epigenetic responses to regulatory perturbations in cancer cells and the associations between transcription factor binding profiles.

scholarly journals Variation in VKORC1 Is Associated with Vascular Dementia

2021 ◽  
Vol 80 (3) ◽  
pp. 1329-1337
Author(s):  
Jure Mur ◽  
Daniel L. McCartney ◽  
Daniel I. Chasman ◽  
Peter M. Visscher ◽  
Graciela Muniz-Terrera ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Vascular Dementia ◽  
Genetic Variant ◽  
Warfarin Dose ◽  
Uk Biobank ◽  
Parental History ◽  
Genome Wide ◽  
History Of ◽  
First Time ◽  
The Relationship

Background: The genetic variant rs9923231 (VKORC1) is associated with differences in the coagulation of blood and consequentially with sensitivity to the drug warfarin. Variation in VKORC1 has been linked in a gene-based test to dementia/Alzheimer’s disease in the parents of participants, with suggestive evidence for an association for rs9923231 (p = 1.8×10–7), which was included in the genome-wide significant KAT8 locus. Objective: Our study aimed to investigate whether the relationship between rs9923231 and dementia persists only for certain dementia sub-types, and if those taking warfarin are at greater risk. Methods: We used logistic regression and data from 238,195 participants from UK Biobank to examine the relationship between VKORC1, risk of dementia, and the interplay with warfarin use. Results: Parental history of dementia, APOE variant, atrial fibrillation, diabetes, hypertension, and hypercholesterolemia all had strong associations with vascular dementia (p < 4.6×10–6). The T-allele in rs9923231 was linked to a lower warfarin dose (βperT - allele = –0.29, p < 2×10–16) and risk of vascular dementia (OR = 1.17, p = 0.010), but not other dementia sub-types. However, the risk of vascular dementia was not affected by warfarin use in carriers of the T-allele. Conclusion: Our study reports for the first time an association between rs9923231 and vascular dementia, but further research is warranted to explore potential mechanisms and specify the relationship between rs9923231 and features of vascular dementia.

scholarly journals Genome-Wide Transcriptomic Analysis of Non-Tumorigenic Tissues Reveals Aging-Related Prognostic Markers and Drug Targets in Renal Cell Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 3045
Author(s):  
Euiyoung Oh ◽  
Jun-Hyeong Kim ◽  
JungIn Um ◽  
Da-Woon Jung ◽  
Darren R. Williams ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cancer Patient ◽  
Immune Cells ◽  
Renal Cell ◽  
Prognostic Markers ◽  
Patient Survival ◽  
Survival Outcome ◽  
Normal Tissues ◽  
Genome Wide ◽  
The Relationship

The relationship between expression of aging-related genes in normal tissues and cancer patient survival has not been assessed. We developed a genome-wide transcriptomic analysis approach for normal tissues adjacent to the tumor to identify aging-related transcripts associated with survival outcome, and applied it to 12 cancer types. As a result, five aging-related genes (DUSP22, MAPK14, MAPKAPK3, STAT1, and VCP) in normal tissues were found to be significantly associated with a worse survival outcome in patients with renal cell carcinoma (RCC). This computational approach was investigated using nontumorigenic immune cells purified from young and aged mice. Aged immune cells showed upregulated expression of all five aging-related genes and promoted RCC invasion compared to young immune cells. Further studies revealed DUSP22 as a regulator and druggable target of metastasis. DUSP22 gene knockdown reduced RCC invasion and the small molecule inhibitor BML-260 prevented RCC dissemination in a tumor/immune cell xenograft model. Overall, these results demonstrate that deciphering the relationship between aging-related gene expression in normal tissues and cancer patient survival can provide new prognostic markers, regulators of tumorigenesis and novel targets for drug development.

scholarly journals Genome-Wide Identification and Genetic Variations of the Starch Synthase Gene Family in Rice

Plants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1154
Author(s):  
Hongjia Zhang ◽  
Seong-Gyu Jang ◽  
San Mar Lar ◽  
Ah-Rim Lee ◽  
Fang-Yuan Cao ◽  
...  
Keyword(s):  
Gene Family ◽  
Catalytic Domain ◽  
Amylose Content ◽  
Expression Patterns ◽  
Starch Synthase ◽  
Eating Quality ◽  
Segmental Duplications ◽  
Genome Wide ◽  
The Relationship

Starch is a major ingredient in rice, and the amylose content of starch significantly impacts rice quality. OsSS (starch synthase) is a gene family related to the synthesis of amylose and amylopectin, and 10 members have been reported. In the present study, a synteny analysis of a novel family member belonging to the OsSSIV subfamily that contained a starch synthase catalytic domain showed that three segmental duplications and multiple duplications were identified in rice and other species. Expression data showed that the OsSS gene family is involved in diverse expression patterns. The prediction of miRNA targets suggested that OsSS are possibly widely regulated by miRNA functions, with miR156s targeted to OsSSII-3, especially. Haplotype analysis exhibited the relationship between amylose content and diverse genotypes. These results give new insight and a theoretical basis for the improved amylose content and eating quality of rice.

scholarly journals Prediction of genome-wide effects of single nucleotide variants on transcription factor binding

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Sebastian Carrasco Pro ◽  
Katia Bulekova ◽  
Brian Gregor ◽  
Adam Labadorf ◽  
Juan Ignacio Fuxman Bass
Keyword(s):  
Binding Sites ◽  
Cancer Type ◽  
Single Nucleotide Variants ◽  
Single Nucleotide ◽  
Regulatory Regions ◽  
Genome Wide ◽  
Transcriptional Regulatory ◽  
Gene Regulatory ◽  
The Impact ◽  
The Relationship

Abstract Single nucleotide variants (SNVs) located in transcriptional regulatory regions can result in gene expression changes that lead to adaptive or detrimental phenotypic outcomes. Here, we predict gain or loss of binding sites for 741 transcription factors (TFs) across the human genome. We calculated ‘gainability’ and ‘disruptability’ scores for each TF that represent the likelihood of binding sites being created or disrupted, respectively. We found that functional cis-eQTL SNVs are more likely to alter TF binding sites than rare SNVs in the human population. In addition, we show that cancer somatic mutations have different effects on TF binding sites from different TF families on a cancer-type basis. Finally, we discuss the relationship between these results and cancer mutational signatures. Altogether, we provide a blueprint to study the impact of SNVs derived from genetic variation or disease association on TF binding to gene regulatory regions.

Sign in / Sign up

Export Citation Format

Share Document