Data of epigenomic profiling of histone marks and CTCF binding sites in bovine rumen epithelial primary cells before and after butyrate treatment

The transcription factor FoxO3 regulates multiple genes involved in cell resilience. We have previously implicated variation in non-coding DNA of the FoxO3 gene ( FOXO3 ) with lower blood pressure, reduced inflammation, less hypertension, reduced coronary heart disease mortality, and longevity. The aim of the present study was to determine transcriptional, genetic and genomic mechanisms involving FOXO3 . By DNA sequencing of chromosome 6q21 in lymphoblastoid cell lines of 95 men who had survived to ≥ 95 years of age we identified 110 FOXO3 single nucleotide polymorphisms (SNPs). Thirteen SNPs were at binding sites for 18 transcription factors. Those SNPs appeared to be in physical contact, via RNA polymerase II binding chromatin looping, with sites in the FOXO3 promoter, and likely function together as a cis -regulatory unit. At the chromosome level, FOXO3 was located at the center of a 7.3 Mb 46-gene chromatin domain flanked by gene deserts. We identified distant contact points between FOXO3 and these 46 neighboring genes, through long-range physical contacts via CCCTC-binding factor zinc finger protein (CTCF) binding sites. The genes in this “archipelago” of neighbourhood genes mediate a similar repertoire of functions as FoxO3, including stress resistance, nutrient sensing, cell proliferation, autophagy, apoptosis and stem cell maintenance. The 7.3 Mb gene domain was highly conserved across species, indicating evolutionary importance. We believe that FOXO3 serves as the hub for an “interactome” involved in healthy aging, including cardiovascular disease reduction, in those with favorable FOXO3 genotypes. In support, we found that cellular stress (H 2 O 2 ) could stimulate FOXO3 expression in 20 lymphoblastoid cell lines, being 3-fold stronger for those with a favorable FOXO3 genotype. In FISH experiments, stress-induced activation of FOXO3 caused it to move towards its neighboring genes as suggested by our genomic data. In conclusion, we have shown, for the first time, that FOXO3 is at the central hub of a gene network on chromosome 6 involved in cell protection and healthy aging. The concept of “gene factories” may apply more broadly to genome and genetic mechanisms involved in cardiovascular disease etiology.

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Chromatin extrusion explains key features of loop and domain formation in wild-type and engineered genomes

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1518552112 ◽

2015 ◽

Vol 112 (47) ◽

pp. E6456-E6465 ◽

Cited By ~ 857

Author(s):

Adrian L. Sanborn ◽

Suhas S. P. Rao ◽

Su-Chen Huang ◽

Neva C. Durand ◽

Miriam H. Huntley ◽

...

Keyword(s):

Genome Editing ◽

Binding Sites ◽

Physical Structure ◽

Ctcf Binding ◽

Binding Motifs ◽

Physical Simulations ◽

Chromatin Folding ◽

Mammalian Genomes ◽

Single Base Pair ◽

Fractal Globule

We recently used in situ Hi-C to create kilobase-resolution 3D maps of mammalian genomes. Here, we combine these maps with new Hi-C, microscopy, and genome-editing experiments to study the physical structure of chromatin fibers, domains, and loops. We find that the observed contact domains are inconsistent with the equilibrium state for an ordinary condensed polymer. Combining Hi-C data and novel mathematical theorems, we show that contact domains are also not consistent with a fractal globule. Instead, we use physical simulations to study two models of genome folding. In one, intermonomer attraction during polymer condensation leads to formation of an anisotropic “tension globule.” In the other, CCCTC-binding factor (CTCF) and cohesin act together to extrude unknotted loops during interphase. Both models are consistent with the observed contact domains and with the observation that contact domains tend to form inside loops. However, the extrusion model explains a far wider array of observations, such as why loops tend not to overlap and why the CTCF-binding motifs at pairs of loop anchors lie in the convergent orientation. Finally, we perform 13 genome-editing experiments examining the effect of altering CTCF-binding sites on chromatin folding. The convergent rule correctly predicts the affected loops in every case. Moreover, the extrusion model accurately predicts in silico the 3D maps resulting from each experiment using only the location of CTCF-binding sites in the WT. Thus, we show that it is possible to disrupt, restore, and move loops and domains using targeted mutations as small as a single base pair.

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Functions of Gtf2i and Gtf2ird1 in the developing brain: transcription, DNA-binding, and long term behavioral consequences

10.1101/854851 ◽

2019 ◽

Author(s):

Nathan D. Kopp ◽

Kayla R. Nygaard ◽

Katherine B. McCullough ◽

Susan E. Maloney ◽

Harrison W. Gabel ◽

...

Keyword(s):

Dna Binding ◽

Binding Sites ◽

Conditioned Fear ◽

Developing Brain ◽

Ctcf Binding ◽

Microdeletion Syndrome ◽

Behavioral Phenotypes ◽

Marble Burying ◽

And Behavior

AbstractGtf2ird1 and Gtf2i may mediate aspects of the cognitive and behavioral phenotypes of Williams Syndrome (WS) – a microdeletion syndrome encompassing these transcription factors (TFs). Knockout mouse models of each TF show behavioral phenotypes. Here we identify their genomic binding sites in the developing brain, and test for additive effects of their mutation on transcription and behavior. Both TFs target constrained chromatin modifier and synaptic protein genes, including a significant number of ASD genes. They bind promoters, strongly overlap CTCF binding and TAD boundaries, and moderately overlap each other, suggesting epistatic effects. We used single and double mutants to test whether mutating both TFs will modify transcriptional and behavioral phenotypes of single Gtf2ird1 mutants. Despite little difference in DNA-binding and transcriptome-wide expression, Gtf2ird1 mutation caused balance, marble burying, and conditioned fear phenotypes. However, mutating Gtf2i in addition to Gtf2ird1 did not further modify transcriptomic or most behavioral phenotypes, suggesting Gtf2ird1 mutation alone is sufficient.

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Rapid and Low-Input Profiling of Histone Marks in Plants Using Nucleus CUT&Tag

Frontiers in Plant Science ◽

10.3389/fpls.2021.634679 ◽

2021 ◽

Vol 12 ◽

Author(s):

Weizhi Ouyang ◽

Xiwen Zhang ◽

Yong Peng ◽

Qing Zhang ◽

Zhilin Cao ◽

...

Keyword(s):

Histone Modifications ◽

Chromatin Immunoprecipitation ◽

Binding Sites ◽

Protein A ◽

Transcriptional Factor ◽

Experimental Procedure ◽

Histone Marks ◽

Genome Wide ◽

Efficient Alternative ◽

Tn5 Transposase

Characterizing genome-wide histone posttranscriptional modifications and transcriptional factor occupancy is crucial for deciphering their biological functions. Chromatin immunoprecipitation followed by sequencing (ChIP-seq) is a powerful method for genome-wide profiling of histone modifications and transcriptional factor-binding sites. However, the current ChIP-seq experimental procedure in plants requires significant material and several days for completion. CUT&Tag is an alternative method of ChIP-seq for low-sample and single-cell epigenomic profiling using protein A-Tn5 transposase fusion proteins (PAT). In this study, we developed a nucleus CUT&Tag (nCUT&Tag) protocol based on the live-cell CUT&Tag technology. Our results indicate that nCUT&Tag could be used for histone modifications profiling in both monocot rice and dicot rapeseed using crosslinked or fresh tissues. In addition, both active and repressive histone marks such as H3K4me3 and H3K9me2 can be identified using our nCUT&Tag. More importantly, all the steps in nCUT&Tag can be finished in only 1 day, and the assay can be performed with as little as 0.01 g of plant tissue as starting materials. Therefore, our results demonstrate that nCUT&Tag is an efficient alternative strategy for plant epigenomic studies.

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CTCF and cohesin promote focal detachment of DNA from the nuclear lamina

10.1101/2021.09.13.460079 ◽

2021 ◽

Author(s):

Tom van Schaik ◽

Ning Qing Liu ◽

Stefano G. Manzo ◽

Daan Peric-Hupkes ◽

Elzo de Wit ◽

...

Keyword(s):

Stem Cells ◽

Histone Modifications ◽

Binding Sites ◽

Embryonic Stem ◽

Nuclear Lamina ◽

Fine Tuning ◽

Ctcf Binding ◽

Strongly Correlated ◽

Sharp Transition ◽

Genomic Regions

Lamina associated domains (LADs) are large genomic regions that are positioned at the nuclear lamina (NL). It has remained largely unclear what drives the positioning and demarcation of LADs. Because the insulator protein CTCF is enriched at LAD borders, it was postulated that CTCF binding could position a subset of LAD boundaries, possibly through its function in stalling cohesin and hence preventing cohesin to invade into the LAD. To test this, we mapped genome - NL interactions in mouse embryonic stem cells after rapid depletion of CTCF and other perturbations of cohesin dynamics. CTCF and cohesin contribute to a sharp transition in NL interactions at LAD borders, whilst LADs are maintained after depletion of these proteins, also at borders marked by CTCF. CTCF and cohesin may thus reinforce LAD borders, but do not position these. CTCF binding sites within LADs are locally detached from the NL and enriched for accessible DNA and active histone modifications. Remarkably, even though NL positioning is strongly correlated with genome inactivity, this DNA remains accessible after the local detachment is lost following CTCF depletion. At a chromosomal scale, cohesin depletion and cohesin stabilization (depletion of the unloading factor WAPL) quantitatively affect NL interactions, indicative of perturbed chromosomal positioning in the nucleus. Finally, while H3K27me3 is locally enriched at CTCF-marked LAD borders, we find no evidence for an interplay between CTCF and H3K27me3 on NL interactions. Combined, these findings illustrate that CTCF and cohesin do not shape LAD patterns. Rather, these proteins mediate fine-tuning of NL interactions.

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CTCF Recruits Centromeric Protein CENP-E to the Pericentromeric/Centromeric Regions of Chromosomes through Unusual CTCF-Binding Sites

Cell Reports ◽

10.1016/j.celrep.2015.08.005 ◽

2015 ◽

Vol 12 (10) ◽

pp. 1704-1714 ◽

Cited By ~ 11

Author(s):

Tiaojiang Xiao ◽

Patompon Wongtrakoongate ◽

Cecelia Trainor ◽

Gary Felsenfeld

Keyword(s):

Binding Sites ◽

Ctcf Binding ◽

Centromeric Protein

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Comprehensive mapping of the effects of azacitidine on DNA methylation, repressive/permissive histone marks and gene expression in primary cells from patients with MDS and MDS-related disease

Oncotarget ◽

10.18632/oncotarget.15807 ◽

2017 ◽

Vol 8 (17) ◽

pp. 28812-28825 ◽

Cited By ~ 21

Author(s):

Magnus Tobiasson ◽

Hani Abdulkadir ◽

Andreas Lennartsson ◽

Shintaro Katayama ◽

Francesco Marabita ◽

...

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Primary Cells ◽

Histone Marks ◽

Related Disease ◽

Comprehensive Mapping

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An H3K4me3 reader, BAP18 as an adaptor of COMPASS-like core subunits co-activates ERα action and associates with the sensitivity of antiestrogen in breast cancer

Nucleic Acids Research ◽

10.1093/nar/gkaa787 ◽

2020 ◽

Vol 48 (19) ◽

pp. 10768-10784

Author(s):

Ge Sun ◽

Chunyu Wang ◽

Shengli Wang ◽

Hongmiao Sun ◽

Kai Zeng ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Progression ◽

Binding Sites ◽

Estrogen Receptor Alpha ◽

Target Genes ◽

Regulatory Element ◽

Therapy Resistance ◽

Ctcf Binding ◽

Promoter Regions ◽

Positive Breast Cancer

Abstract Estrogen receptor alpha (ERα) signaling pathway is essential for ERα-positive breast cancer progression and endocrine therapy resistance. Bromodomain PHD Finger Transcription Factor (BPTF) associated protein of 18kDa (BAP18) has been recognized as a crucial H3K4me3 reader. However, the whole genomic occupation of BAP18 and its biological function in breast cancer is still elusive. Here, we found that higher expression of BAP18 in ERα-positive breast cancer is positively correlated with poor prognosis. ChIP-seq analysis further demonstrated that the half estrogen response elements (EREs) and the CCCTC binding factor (CTCF) binding sites are the significant enrichment sites found in estrogen-induced BAP18 binding sites. Also, we provide the evidence to demonstrate that BAP18 as a novel co-activator of ERα is required for the recruitment of COMPASS-like core subunits to the cis-regulatory element of ERα target genes in breast cancer cells. BAP18 is recruited to the promoter regions of estrogen-induced genes, accompanied with the enrichment of the lysine 4-trimethylated histone H3 tail (H3K4me3) in the presence of E2. Furthermore, BAP18 promotes cell growth and associates the sensitivity of antiestrogen in ERα-positive breast cancer. Our data suggest that BAP18 facilitates the association between ERα and COMPASS-like core subunits, which might be an essential epigenetic therapeutic target for breast cancer.

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