ArticleMolecular cell2021
Enhancer RNA m6A methylation facilitates transcriptional condensate formation and gene activation.
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Article in Molecular cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 182 papers.
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182citing papers in PubMed
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Who cites it
182 citing papers in PubMed, 258 citations in OpenAlex.
- Decoding chromatin-associated RNA (caRNA) interaction networks: from genome-wide dynamic capture to epigenetic mechanisms in plants and animals.Epigenetics · 2026Review
- Decoding Biomolecular Phase Separation: From Physiological Roles to Pathological Mechanisms and Therapeutic Biomaterials Design.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- BRD4: From molecular understanding to therapeutics development.Molecular cell · 2026Review
- Glucose and Glutamine Deprivation Promotes Breast Cancer Lung Metastasis via BRD4-Dependent Enhancer Activation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Review
- Integrative Transcriptional and Chromatin Analyses Reveal Enhancer-Mediated Regulatory Programs Driving Breast Cancer Metastasis.Molecular cancer research : MCR · 2026Article
- RNA modifications in cancer: regulators of tumor evolution and therapeutic response.Molecular cancer · 2026Review
- Noncoding RNAs are indispensable architects and regulators of biomolecular condensates.Non-coding RNA research · 2026Review
- Regulatory elements on chromatin-associated RNA 15 years beyond RNA epigenetics.Nature chemical biology · 2026Review
- Nuclear mNature chemical biology · 2026Article
- RNA modifications and epigenetic regulation in plants.aBIOTECH · 2026Review
- Functional chromatin signatures premark future lineage-specific enhancers.Cell genomics · 2026Article
- Direct roles of long non-coding RNAs in transcription activation.Nature structural & molecular biology · 2026Review
- Tandem bromodomains of BRD4 cooperatively read poly-acetylated nucleosomes to enhance chromatin engagement and regulate breast cancer phenotypes.bioRxiv : the preprint server for biology · 2026Article
- HSF1 and YTHDC1 enhance DNA repair under heat stress by promoting repair-associated gene expression.Nucleic acids research · 2026Article
- YTHDC1 recognizes METTL16-dependent mProceedings of the National Academy of Sciences of the United States of America · 2026Article
- circTGFBR2(3-6) acts as an assembly platform for RNA-binding protein IGF2BP3 and TGFBR1 mRNA to enhance breast cancer cell plasticity.Cell death and differentiation · 2026Article
- m6A RNA modification and its emerging roles in diseases: recent advances and therapeutic implications.Journal of translational medicine · 2026Review
- Deciphering the eRNA landscape and revealing target aberrant pathways in prostate cancer.BMC cancer · 2026Article
- NNature reviews. Cancer · 2026Review
122 more citing papers are in PubMed but not listed here.
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Authors and funding
25 authors at 6 institutions in 2 countries.
Joo-Hyung LeeDepartment of Biochemistry and Molecular Biology, McGovern Medical School, University of Texas Health Science Center, Houston, TX 77030, USA.
Ruoyu WangDepartment of Biochemistry and Molecular Biology, McGovern Medical School, University of Texas Health Science Center, Houston, TX 77030, USA; Graduate School of Biomedical Sciences, University of Texas MD Anderson Cancer Center and UTHealth, Houston, TX 77030, USA.
Feng XiongDepartment of Biochemistry and Molecular Biology, McGovern Medical School, University of Texas Health Science Center, Houston, TX 77030, USA.
Joanna KrakowiakDepartment of Biochemistry and Molecular Biology, McGovern Medical School, University of Texas Health Science Center, Houston, TX 77030, USA.
Zian LiaoDepartment of Biochemistry and Molecular Biology, McGovern Medical School, University of Texas Health Science Center, Houston, TX 77030, USA; Graduate School of Biomedical Sciences, University of Texas MD Anderson Cancer Center and UTHealth, Houston, TX 77030, USA.
Phuoc T NguyenDepartment of Biochemistry and Molecular Biology, McGovern Medical School, University of Texas Health Science Center, Houston, TX 77030, USA; Graduate School of Biomedical Sciences, University of Texas MD Anderson Cancer Center and UTHealth, Houston, TX 77030, USA.
Elena V Moroz-OmoriDepartment of Biochemistry, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
Jiaofang ShaoDepartment of Biochemistry and Molecular Biology, McGovern Medical School, University of Texas Health Science Center, Houston, TX 77030, USA.
Xiaoyu ZhuDepartment of Biochemistry and Molecular Biology, McGovern Medical School, University of Texas Health Science Center, Houston, TX 77030, USA.
Michael J BoltInstitute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, TX 77030, USA; Gulf Coast Consortia Center for Advanced Microscopy and Image Informatics, Houston, TX 77030, USA.
Haoyi WuDepartment of Biochemistry and Molecular Biology, McGovern Medical School, University of Texas Health Science Center, Houston, TX 77030, USA; Graduate School of Biomedical Sciences, University of Texas MD Anderson Cancer Center and UTHealth, Houston, TX 77030, USA.
Pankaj K SinghInstitute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, TX 77030, USA; Gulf Coast Consortia Center for Advanced Microscopy and Image Informatics, Houston, TX 77030, USA.
Mingjun BiDepartment of Molecular Medicine, Mays Cancer Center, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
Caleb J ShiDepartment of Biochemistry and Molecular Biology, McGovern Medical School, University of Texas Health Science Center, Houston, TX 77030, USA.
Naadir JamalDepartment of Biochemistry and Molecular Biology, McGovern Medical School, University of Texas Health Science Center, Houston, TX 77030, USA.
Guojie LiDepartment of Biochemistry and Molecular Biology, McGovern Medical School, University of Texas Health Science Center, Houston, TX 77030, USA.
Ragini MistryGulf Coast Consortia Center for Advanced Microscopy and Image Informatics, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Sung Yun JungVerna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Kuang-Lei TsaiDepartment of Biochemistry and Molecular Biology, McGovern Medical School, University of Texas Health Science Center, Houston, TX 77030, USA.
Josephine C FerreonDepartment of Pharmacology and Chemical Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Fabio StossiGulf Coast Consortia Center for Advanced Microscopy and Image Informatics, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Amedeo CaflischDepartment of Biochemistry, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
Zhijie LiuDepartment of Molecular Medicine, Mays Cancer Center, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
Michael A ManciniInstitute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, TX 77030, USA; Gulf Coast Consortia Center for Advanced Microscopy and Image Informatics, Houston, TX 77030, USA; Department of Pharmacology and Chemical Biology, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.
Wenbo LiDepartment of Biochemistry and Molecular Biology, McGovern Medical School, University of Texas Health Science Center, Houston, TX 77030, USA; Graduate School of Biomedical Sciences, University of Texas MD Anderson Cancer Center and UTHealth, Houston, TX 77030, USA. Electronic address: wenbo.li@uth.tmc.edu.
The University of Texas Health Science Center at Houston · USThe University of Texas MD Anderson Cancer Center · USBaylor College of Medicine · USTexas A&M Health Science Center · USThe University of Texas Health Science Center at San Antonio · USUniversity of Zurich · CH
Funding
Tumor BiologyP30CA125123 · NCI · BAYLOR COLLEGE OF MEDICINE · PI Michael M Ittmann · 2007 to 2026
$73.9MConvalescent Plasma to Limit Coronavirus Associated ComplicationsUL1TR003167 · NCATS · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI KARP, DANIEL D, MCPHERSON, DAVID D · 2019 to 2023
$45.3MTissue Analysis & Molecular Imaging CoreP30DK056338 · NIDDK · BAYLOR COLLEGE OF MEDICINE · PI James Versalovic · 2001 to 2026
$28.3MTranslational Research Support CoreP30ES030285 · NIEHS · BAYLOR COLLEGE OF MEDICINE · PI Casey W Wright · 2019 to 2026
$14.7MStructure and Functionof Nanog in Stem Cell PluripotencyR01GM122763 · NIGMS · BAYLOR COLLEGE OF MEDICINE · PI Josephine Chu Ferreon · 2018 to 2026
$3.4MBeyond Gene Dosage: Understanding Down Syndrome via 4D Genome OrganizationU01HL156059 · NHLBI · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI LI, WENBO · 2020 to 2024
$3.1MMechanisms Underlying Enhancer Rnp Mediated Gene Regulation And Genome OrganizationR01GM136922 · NIGMS · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI LI, WENBO · 2020 to 2024
$2.0MNovel Coregulators of Estrogen Receptor in Enhancer-regulated TranscriptionR01GM137009 · NIGMS · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI LIU, ZHIJIE "JASON" · 2020 to 2023
$1.0MCondensin-mediated enhancer and chromatin architectural control of breast cancer gene transcriptionK22CA204468 · NCI · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI LI, WENBO · 2017 to 2019
$486kOptogenetic Engineering of 3D Chromatin ArchitectureR21GM132778 · NIGMS · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI LI, WENBO · 2019 to 2020
$434kNCATS NIH HHS UL1 TR003167NCI NIH HHS K22 CA204468NCI NIH HHS P30 CA125123NHLBI NIH HHS U01 HL156059NIDDK NIH HHS P30 DK056338NIEHS NIH HHS P30 ES030285NIGMS NIH HHS R01 GM122763NIGMS NIH HHS R01 GM136922NIGMS NIH HHS R01 GM137009NIGMS NIH HHS R21 GM132778
Abstract
The mechanistic understanding of nascent RNAs in transcriptional control remains limited. Here, by a high sensitivity method methylation-inscribed nascent transcripts sequencing (MINT-seq), we characterized the landscapes of N6-methyladenosine (m6A) on nascent RNAs. We uncover heavy but selective m6A deposition on nascent RNAs produced by transcription regulatory elements, including promoter upstream antisense RNAs and enhancer RNAs (eRNAs), which positively correlates with their length, inclusion of m6A motif, and RNA abundances. m6A-eRNAs mark highly active enhancers, where they recruit nuclear m6A reader YTHDC1 to phase separate into liquid-like condensates, in a manner dependent on its C terminus intrinsically disordered region and arginine residues. The m6A-eRNA/YTHDC1 condensate co-mixes with and facilitates the formation of BRD4 coactivator condensate. Consequently, YTHDC1 depletion diminished BRD4 condensate and its recruitment to enhancers, resulting in inhibited enhancer and gene activation. We propose that chemical modifications of eRNAs together with reader proteins play broad roles in enhancer activation and gene transcriptional control.
Indexed as
AdenosineBromodomain Containing ProteinsCell Cycle ProteinsEnhancer Elements, GeneticGene Expression RegulationHumansMethylationNerve Tissue ProteinsRegulatory Elements, TranscriptionalRNARNA Splicing FactorsTranscriptional ActivationTranscription FactorsAdenosineBRD4 protein, humanBromodomain Containing ProteinsCell Cycle ProteinsNerve Tissue ProteinsN-methyladenosineRNARNA Splicing FactorsTranscription FactorsYTHDC1 protein, humanBRD4enhancer RNAsenhancersepitranscriptomeMINT-Seqnuclear condensatephase separationRNA m6A methylationtranscriptional activationYTHDC1
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