Functional footprinting of regulatory DNA

Vierstra, Jeff; Reik, Andreas; Chang, Kai Hsin; Stehling-Sun, Sandra; Zhou, Yuanyue; Hinkley, Sarah J.; Paschon, David E.; Zhang, Lei; Psatha, Nikoletta; Bendaña, Yuri R.; O’Neil, Colleen M.; Song, Alexander H.; Mich, Andrea; Liu, Pei Qi; Lee, Gary; Bauer, Daniel E.; Holmes, Michael C.; Orkin, Stuart H.; Papayannopoulou, Thalia; Stamatoyannopoulos, George; Rebar, Edward J.; Gregory, Philip D.; Urnov, Fyodor D.; Stamatoyannopoulos, J

doi:10.1038/nmeth.3554

Cited by 127 publications

(101 citation statements)

References 23 publications

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“…Particularly in plants, these TF-associated CRE enrichment positions can be used together with known CPEs to accurately predict the locations of TSS peaks of all three types (but known plant CPEs alone cannot accurately predict TSS location) (Morton et al, 2014). Interestingly, regions of open chromatin (OC) are proving useful to identify functional CRE sites (Song and Crawford, 2010;Song et al, 2011;Vierstra et al, 2015), yet are not required to accurately predict a highly expressed TSS location (Morton et al, 2015). It may well be the case that knowledge of OC regions are a necessary component to understanding the tissue, time, and/or level at which a given promoter region will express.…”

Section: The State Of the Core: Our Limited Knowledge Of Pol II Core mentioning

confidence: 99%

Small Genetic Circuits and MicroRNAs: Big Players in Polymerase II Transcriptional Control in Plants

et al. 2016

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ORCID IDs: 0000-0001-6793-6151 (M.M.); 0000-0002-0105-6431 (S.A.F.)RNA Polymerase II (Pol II) regulatory cascades involving transcription factors (TFs) and their targets orchestrate the genetic circuitry of every eukaryotic organism. In order to understand how these cascades function, they can be dissected into small genetic networks, each containing just a few Pol II transcribed genes, that generate specific signal-processing outcomes. Small RNA regulatory circuits involve direct regulation of a small RNA by a TF and/or direct regulation of a TF by a small RNA and have been shown to play unique roles in many organisms. Here, we will focus on small RNA regulatory circuits containing Pol II transcribed microRNAs (miRNAs). While the role of miRNA-containing regulatory circuits as modular building blocks for the function of complex networks has long been on the forefront of studies in the animal kingdom, plant studies are poised to take a lead role in this area because of their advantages in probing transcriptional and posttranscriptional control of Pol II genes. The relative simplicity of tissue-and cell-type organization, miRNA targeting, and genomic structure make the Arabidopsis thaliana plant model uniquely amenable for small RNA regulatory circuit studies in a multicellular organism. In this Review, we cover analysis, tools, and validation methods for probing the component interactions in miRNA-containing regulatory circuits. We then review the important roles that plant miRNAs are playing in these circuits and summarize methods for the identification of small genetic circuits that strongly influence plant function. We conclude by noting areas of opportunity where new plant studies are imminently needed.

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Section: The State Of the Core: Our Limited Knowledge Of Pol II Core mentioning

confidence: 99%

Small Genetic Circuits and MicroRNAs: Big Players in Polymerase II Transcriptional Control in Plants

et al. 2016

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“…2a). These reagents can bypass the epigenetic constraints of gene expression within a cell and have been used for a variety of genomewide screens to efficiently silence either single or multiple genes or silence the influence of regulatory domains in the native genomic context 49, 50, 51, 52, 53, 54, 55, 56, 57, 58.…”

Section: Dna Methylation and Demethylationmentioning

confidence: 99%

CRISPR-based reagents to study the influence of the epigenome on gene expression

Lavender

Kelly

Hendy

et al. 2018

Clinical and Experimental Immunology

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SummaryThe use of epigenome editing is set to expand our knowledge of how epigenetic landscapes facilitate gene expression capacity within a given cell. As epigenetic landscape profiling in health and disease becomes more commonplace, so does the requirement to assess the functional impact that particular regulatory domains and DNA methylation profiles have upon gene expression capacity. That functional assessment is particularly pertinent when analysing epigenomes in disease states where the reversible nature of histone and DNA modification might yield plausible therapeutic targets. In this review we discuss first the nature of the epigenetic landscape, secondly the types of factors that deposit and erase the various modifications, consider how modifications transduce their signals, and lastly address current tools for experimental epigenome editing with particular emphasis on the immune system.

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“…57 Methodical perturbation of regulatory sequences, such as the fetal hemoglobinassociated erythroid-specific enhancer of BCL11A 58 by CRISPR/Cas9 and ZFN/TALEN mutagenesis, have identified critical regulatory sequences that themselves may serve as therapeutic targets. 59,60 In contrast to conventional genome editing, which implies permanent modification of genomic target sequences, genome editing tools may be repurposed to engender potent biological outcomes without mutagenesis. For example, catalytically inactive mutants of Cas9 (dCas9) may be guided to proximal promoters or coding sequences to block transcription.…”

Section: 46-51mentioning

confidence: 99%

A genome editing primer for the hematologist

Hoban

Bauer

2016

Blood

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Gene editing enables the site-specific modification of the genome. These technologies have rapidly advanced such that they have entered common use in experimental hematology to investigate genetic function. In addition, genome editing is becoming increasingly plausible as a treatment modality to rectify genetic blood disorders and improve cellular therapies. Genome modification typically ensues from site-specific double-strand breaks and may result in a myriad of outcomes. Even single-strand nicks and targeted biochemical modifications that do not permanently alter the DNA sequence (epigenome editing) may be powerful instruments. In this review, we examine the various technologies, describe their advantages and shortcomings for engendering useful genetic alterations, and consider future prospects for genome editing to impact hematology.

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Functional footprinting of regulatory DNA

Cited by 127 publications

References 23 publications

Small Genetic Circuits and MicroRNAs: Big Players in Polymerase II Transcriptional Control in Plants

Small Genetic Circuits and MicroRNAs: Big Players in Polymerase II Transcriptional Control in Plants

CRISPR-based reagents to study the influence of the epigenome on gene expression

A genome editing primer for the hematologist

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