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Article Dans Une Revue Nucleic Acids Research Année : 2024

Simultaneous profiling of chromatin accessibility and DNA methylation in complete plant genomes using long-read sequencing

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Abstract Epigenetic regulations, including chromatin accessibility, nucleosome positioning and DNA methylation intricately shape genome function. However, current chromatin profiling techniques relying on short-read sequencing technologies fail to characterise highly repetitive genomic regions and cannot detect multiple chromatin features simultaneously. Here, we performed Simultaneous Accessibility and DNA Methylation Sequencing (SAM-seq) of purified plant nuclei. Thanks to the use of long-read nanopore sequencing, SAM-seq enables high-resolution profiling of m6A-tagged chromatin accessibility together with endogenous cytosine methylation in plants. Analysis of naked genomic DNA revealed significant sequence preference biases of m6A-MTases, controllable through a normalisation step. By applying SAM-seq to Arabidopsis and maize nuclei we obtained fine-grained accessibility and DNA methylation landscapes genome-wide. We uncovered crosstalk between chromatin accessibility and DNA methylation within nucleosomes of genes, TEs, and centromeric repeats. SAM-seq also detects DNA footprints over cis-regulatory regions. Furthermore, using the single-molecule information provided by SAM-seq we identified extensive cellular heterogeneity at chromatin domains with antagonistic chromatin marks, suggesting that bivalency reflects cell-specific regulations. SAM-seq is a powerful approach to simultaneously study multiple epigenetic features over unique and repetitive sequences, opening new opportunities for the investigation of epigenetic mechanisms.
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hal-04581837 , version 1 (21-05-2024)

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Basile Leduque, Alejandro Edera, Clémentine Vitte, Leandro Quadrana. Simultaneous profiling of chromatin accessibility and DNA methylation in complete plant genomes using long-read sequencing. Nucleic Acids Research, 2024, 1 (13), ⟨10.1093/nar/gkae306⟩. ⟨hal-04581837⟩
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