Huang et al. 2019 (PRJNA501872)

General Details

Title Active ribosome profiling in SETD2 or METTL14 knockdown HepG2 cells
Organism
Number of Samples 24
Release Date 2018/10/29 00:00
Sequencing Types
Protocol Details

Study Links

Repository Details

SRA SRP167238
ENA SRP167238
GEO GSE121952
BioProject PRJNA501872

Publication

Title
Authors Huang H, Weng H, Zhou K, Wu T, Zhao BS, Sun M, Chen Z, Deng X, Xiao G, Auer F, Klemm L, Wu H, Zuo Z, Qin X, Dong Y, Zhou Y, Qin H, Tao S, Du J, Liu J, Lu Z, Yin H, Mesquita A, Yuan CL, Hu YC, Sun W, Su R, Dong L, Shen C, Li C, Qing Y, Jiang X, Wu X, Sun M, Guan JL, Qu L, Wei M, Müschen M, Huang G, He C, Yang J, Chen J
Journal Nature
Publication Date 2019 Mar
Abstract DNA and histone modifications have notable effects on gene expression 1 . Being the most prevalent internal modification in mRNA, the N 6 -methyladenosine (m 6 A) mRNA modification is as an important post-transcriptional mechanism of gene regulation 2-4 and has crucial roles in various normal and pathological processes 5-12 . However, it is unclear how m 6 A is specifically and dynamically deposited in the transcriptome. Here we report that histone H3 trimethylation at Lys36 (H3K36me3), a marker for transcription elongation, guides m 6 A deposition globally. We show that m 6 A modifications are enriched in the vicinity of H3K36me3 peaks, and are reduced globally when cellular H3K36me3 is depleted. Mechanistically, H3K36me3 is recognized and bound directly by METTL14, a crucial component of the m 6 A methyltransferase complex (MTC), which in turn facilitates the binding of the m 6 A MTC to adjacent RNA polymerase II, thereby delivering the m 6 A MTC to actively transcribed nascent RNAs to deposit m 6 A co-transcriptionally. In mouse embryonic stem cells, phenocopying METTL14 knockdown, H3K36me3 depletion also markedly reduces m 6 A abundance transcriptome-wide and in pluripotency transcripts, resulting in increased cell stemness. Collectively, our studies reveal the important roles of H3K36me3 and METTL14 in determining specific and dynamic deposition of m 6 A in mRNA, and uncover another layer of gene expression regulation that involves crosstalk between histone modification and RNA methylation.
PMC PMC6438714
PMID 30867593
DOI
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)
SRR8135324 PRJNA501872 Homo sapiens HepG2 RNA-Seq Cycloheximide
SRR8135325 PRJNA501872 Homo sapiens HepG2 RNA-Seq Cycloheximide
SRR8135326 PRJNA501872 Homo sapiens HepG2 RNA-Seq Cycloheximide
SRR8135327 PRJNA501872 Homo sapiens HepG2 RNA-Seq Cycloheximide
SRR8135328 PRJNA501872 Homo sapiens HepG2 RNA-Seq Cycloheximide
SRR8135329 PRJNA501872 Homo sapiens HepG2 RNA-Seq Cycloheximide
SRR8135330 PRJNA501872 Homo sapiens HepG2 RNA-Seq Cycloheximide
SRR8135331 PRJNA501872 Homo sapiens HepG2 RNA-Seq Cycloheximide
SRR8135332 PRJNA501872 Homo sapiens HepG2 RNA-Seq Cycloheximide
SRR8135333 PRJNA501872 Homo sapiens HepG2 RNA-Seq Cycloheximide
SRR8135334 PRJNA501872 Homo sapiens HepG2 RNA-Seq Cycloheximide
SRR8135335 PRJNA501872 Homo sapiens HepG2 RNA-Seq Cycloheximide
SRR8135336 PRJNA501872 Homo sapiens HepG2 Ribo-Seq Cycloheximide
SRR8135337 PRJNA501872 Homo sapiens HepG2 Ribo-Seq Cycloheximide
SRR8135338 PRJNA501872 Homo sapiens HepG2 Ribo-Seq Cycloheximide
SRR8135339 PRJNA501872 Homo sapiens HepG2 Ribo-Seq Cycloheximide
SRR8135340 PRJNA501872 Homo sapiens HepG2 Ribo-Seq Cycloheximide
SRR8135341 PRJNA501872 Homo sapiens HepG2 Ribo-Seq Cycloheximide
SRR8135342 PRJNA501872 Homo sapiens HepG2 Ribo-Seq Cycloheximide
SRR8135343 PRJNA501872 Homo sapiens HepG2 Ribo-Seq Cycloheximide
SRR8135344 PRJNA501872 Homo sapiens HepG2 Ribo-Seq Cycloheximide
SRR8135345 PRJNA501872 Homo sapiens HepG2 Ribo-Seq Cycloheximide
SRR8135346 PRJNA501872 Homo sapiens HepG2 Ribo-Seq Cycloheximide
SRR8135347 PRJNA501872 Homo sapiens HepG2 Ribo-Seq Cycloheximide
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)

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