H3K4me1 Distribution Predicts Transcription State and Poising at Promoters

Bae, Sunhee; Lesch, Bluma J.

doi:10.3389/fcell.2020.00289

Cited by 74 publications

(92 citation statements)

References 39 publications

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“…H3K4Me3 had the highest intensity consistent with expectations (Guenther et al, 2007) followed by H3K27ac. Some studies show a bimodal distribution of H3K4Me1 and/or H3K4Me3 signal at promoters (Barski et al, 2007;Kingsley et al, 2020) but this is not always observed (Hoffman et al, 2010;Bae and Lesch, 2020). In this study only a very slight bimodal distribution in the profile of H3K4Me3, H3K4Me1, and H3K27ac was observed.…”

Section: Discussioncontrasting

confidence: 61%

Putative Causal Variants Are Enriched in Annotated Functional Regions From Six Bovine Tissues

et al. 2021

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Genetic variants which affect complex traits (causal variants) are thought to be found in functional regions of the genome. Identifying causal variants would be useful for predicting complex trait phenotypes in dairy cows, however, functional regions are poorly annotated in the bovine genome. Functional regions can be identified on a genome-wide scale by assaying for post-translational modifications to histone proteins (histone modifications) and proteins interacting with the genome (e.g., transcription factors) using a method called Chromatin immunoprecipitation followed by sequencing (ChIP-seq). In this study ChIP-seq was performed to find functional regions in the bovine genome by assaying for four histone modifications (H3K4Me1, H3K4Me3, H3K27ac, and H3K27Me3) and one transcription factor (CTCF) in 6 tissues (heart, kidney, liver, lung, mammary and spleen) from 2 to 3 lactating dairy cows. Eighty-six ChIP-seq samples were generated in this study, identifying millions of functional regions in the bovine genome. Combinations of histone modifications and CTCF were found using ChromHMM and annotated by comparing with active and inactive genes across the genome. Functional marks differed between tissues highlighting areas which might be particularly important to tissue-specific regulation. Supporting the cis-regulatory role of functional regions, the read counts in some ChIP peaks correlated with nearby gene expression. The functional regions identified in this study were enriched for putative causal variants as seen in other species. Interestingly, regions which correlated with gene expression were particularly enriched for potential causal variants. This supports the hypothesis that complex traits are regulated by variants that alter gene expression. This study provides one of the largest ChIP-seq annotation resources in cattle including, for the first time, in the mammary gland of lactating cows. By linking regulatory regions to expression QTL and trait QTL we demonstrate a new strategy for identifying causal variants in cattle.

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Section: Discussioncontrasting

confidence: 61%

Putative Causal Variants Are Enriched in Annotated Functional Regions From Six Bovine Tissues

et al. 2021

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“…In addition, the TSS clusters located at gene TSS are marked with a bimodal H3K4me1 pattern which indicates active promoters, in contrast to the others that are marked with relatively unimodal H3K4me1 pattern which indicates active enhancers 38,39 . In summary, the SCAFE TSS classifier robustly distinguishes genuine TSS from artifacts.…”

Section: Tss Identification Using Sc-end5-seq Methodsmentioning

confidence: 99%

Profiling of transcribedcis-regulatory elements in single cells

Moody

Kouno

Suzuki

et al. 2021

Preprint

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Profiling of cis-regulatory elements (CREs, mostly promoters and enhancers) in single cells allows the interrogation of the cell-type and -state specific contexts of gene regulation and genetic predisposition to diseases. Here we demonstrate single-cell RNA-5′end-sequencing (sc-end5-seq) methods can detect transcribed CREs (tCREs), enabling simultaneous quantification of gene expression and enhancer activities in a single assay with no extra cost. We show enhancer RNAs can be effectively detected using sc-end5-seq methods with either random or oligo(dT) priming. To analyze tCREs in single cells, we developed SCAFE (Single Cell Analysis of Five-prime Ends) to identify genuine tCREs and analyze their activities (https://github.com/chung-lab/scafe). As compared to accessible CRE (aCRE, based on chromatin accessibility), tCREs are more accurate in predicting CRE interactions by co-activity, more sensitive in detecting shifts in alternative promoter usage and more enriched in diseases heritability. Our results highlight additional dimensions within sc-end5-seq data which can be used for interrogating gene regulation and disease heritability.

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Section: Histone Modifications and The Ntt-mmp-2 Isoform Expressionmentioning

confidence: 99%

“…H3K4me1 is commonly associated with distal enhancers, but it is also present at promoter regions proximal to transcriptional start site ( Cheng et al, 2014 ; Bae and Lesch, 2020 ). Noteworthy, H3K4me1 peak density was recently examined around promoters in human and mouse germ cells ( Bae and Lesch, 2020 ). H3K4me1 was found to exhibit either a bimodal pattern at active promoters, where it flanks H3K4me3, or a unimodal pattern at poised promoters, where it coincides with both H3K4me3 and trimethylation at lysine 27 of histone H3 (H3K27me3).…”

Section: Histone Modifications and The Ntt-mmp-2 Isoform Expressionmentioning

confidence: 99%

“…H3K4me1 was found to exhibit either a bimodal pattern at active promoters, where it flanks H3K4me3, or a unimodal pattern at poised promoters, where it coincides with both H3K4me3 and trimethylation at lysine 27 of histone H3 (H3K27me3). H3K4me1 distribution was proposed as a key feature of the poised epigenetic state and poising at promoters ( Bae and Lesch, 2020 ).…”

Section: Histone Modifications and The Ntt-mmp-2 Isoform Expressionmentioning

confidence: 99%

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Epigenetic Regulation of the N-Terminal Truncated Isoform of Matrix Metalloproteinase-2 (NTT-MMP-2) and Its Presence in Renal and Cardiac Diseases

et al. 2021

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Several clinical and experimental studies have documented a compelling and critical role for the full-length matrix metalloproteinase-2 (FL-MMP-2) in ischemic renal injury, progressive renal fibrosis, and diabetic nephropathy. A novel N-terminal truncated isoform of MMP-2 (NTT-MMP-2) was recently discovered, which is induced by hypoxia and oxidative stress by the activation of a latent promoter located in the first intron of the MMP2 gene. This NTT-MMP-2 isoform is enzymatically active but remains intracellular in or near the mitochondria. In this perspective article, we first present the findings about the discovery of the NTT-MMP-2 isoform, and its functional and structural differences as compared with the FL-MMP-2 isoform. Based on publicly available epigenomics data from the Encyclopedia of DNA Elements (ENCODE) project, we provide insights into the epigenetic regulation of the latent promoter located in the first intron of the MMP2 gene, which support the activation of the NTT-MMP-2 isoform. We then focus on its functional assessment by covering the alterations found in the kidney of transgenic mice expressing the NTT-MMP-2 isoform. Next, we highlight recent findings regarding the presence of the NTT-MMP-2 isoform in renal dysfunction, in kidney and cardiac diseases, including damage observed in aging, acute ischemia-reperfusion injury (IRI), chronic kidney disease, diabetic nephropathy, and human renal transplants with delayed graft function. Finally, we briefly discuss how our insights may guide further experimental and clinical studies that are needed to elucidate the underlying mechanisms and the role of the NTT-MMP-2 isoform in renal dysfunction, which may help to establish it as a potential therapeutic target in kidney diseases.

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H3K4me1 Distribution Predicts Transcription State and Poising at Promoters

Cited by 74 publications

References 39 publications

Putative Causal Variants Are Enriched in Annotated Functional Regions From Six Bovine Tissues

Putative Causal Variants Are Enriched in Annotated Functional Regions From Six Bovine Tissues

Profiling of transcribedcis-regulatory elements in single cells

Epigenetic Regulation of the N-Terminal Truncated Isoform of Matrix Metalloproteinase-2 (NTT-MMP-2) and Its Presence in Renal and Cardiac Diseases

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