ERNAs Promote Transcription by Establishing Chromatin Accessibility at Defined Genomic Loci

Overview

Journal Mol Cell

Publisher Cell Press

Specialty Cell Biology

Date 2013 Sep 3

PMID 23993744

Citations 287

Authors

Kambiz Mousavi

Hossein Zare

Stefania DellOrso

Lars Grontved

Gustavo Gutierrez-Cruz

Assia Derfoul

Gordon L Hager

Vittorio Sartorelli

Affiliations

Soon will be listed here.

Abstract

Transcription factors and DNA regulatory binding motifs are fundamental components of the gene regulatory network. Here, by using genome-wide binding profiling, we show extensive occupancy of transcription factors of myogenesis (MyoD and Myogenin) at extragenic enhancer regions coinciding with RNA synthesis (i.e., eRNA). In particular, multiple regions were transcribed to eRNA within the regulatory region of MYOD1, including previously characterized distal regulatory regions (DRR) and core enhancer (CE). While (CE)RNA enhanced RNA polymerase II (Pol II) occupancy and transcription at MYOD1, (DRR)RNA acted to activate the downstream myogenic genes. The deployment of transcriptional machinery to appropriate loci is contingent on chromatin accessibility, a rate-limiting step preceding Pol II assembly. By nuclease sensitivity assay, we found that eRNAs regulate genomic access of the transcriptional complex to defined regulatory regions. In conclusion, our data suggest that eRNAs contribute to establishing a cell-type-specific transcriptional circuitry by directing chromatin-remodeling events.

Citing Articles

The Enhancer-Promoter-Mediated Transcription During Neurite Regrowth of Injured Cortical Neurons.

Weng S, Liao W, Chen L Cells. 2025; 14(5).

PMID: 40072048 PMC: 11898497. DOI: 10.3390/cells14050319.

Understanding lncRNAs: key regulators of myogenesis and lipogenesis in farm animals.

Liu W, Chen M, Liu Y, Li X, Li H, Wang J Front Vet Sci. 2025; 12:1540613.

PMID: 40027357 PMC: 11868070. DOI: 10.3389/fvets.2025.1540613.

Application Strategies of Super-Enhancer RNA in Cardiovascular Diseases.

He Y, Cai Y, Cao Y, Wang Y, Wang J, Ding H Biomedicines. 2025; 13(1).

PMID: 39857701 PMC: 11762524. DOI: 10.3390/biomedicines13010117.

A new insight on alleviating the inhibitory effect of aflatoxin B1 on muscle development in grass carp (): The effect of 4-Methylesculetin in vivo and in vitro.

He X, Zhang J, Jiang W, Wu P, Liu Y, Ren H Anim Nutr. 2024; 19:339-354.

PMID: 39640553 PMC: 11617288. DOI: 10.1016/j.aninu.2024.08.001.

Active enhancers: recent research advances and insights into disease.

Zhang J, Wang Q, Liu J, Duan Y, Liu Z, Zhang Z Biol Direct. 2024; 19(1):112.

PMID: 39533395 PMC: 11556110. DOI: 10.1186/s13062-024-00559-x.

References

Joe A, Yi L, Natarajan A, Le Grand F, So L, Wang J . Muscle injury activates resident fibro/adipogenic progenitors that facilitate myogenesis. Nat Cell Biol. 2010; 12(2):153-63. PMC: 4580288. DOI: 10.1038/ncb2015. View

Cosma M . Ordered recruitment: gene-specific mechanism of transcription activation. Mol Cell. 2002; 10(2):227-36. DOI: 10.1016/s1097-2765(02)00604-4. View

Kablar B, Krastel K, Ying C, Asakura A, Tapscott S, Rudnicki M . MyoD and Myf-5 differentially regulate the development of limb versus trunk skeletal muscle. Development. 1998; 124(23):4729-38. DOI: 10.1242/dev.124.23.4729. View

Dean A . On a chromosome far, far away: LCRs and gene expression. Trends Genet. 2005; 22(1):38-45. DOI: 10.1016/j.tig.2005.11.001. View

De Santa F, Barozzi I, Mietton F, Ghisletti S, Polletti S, Tusi B . A large fraction of extragenic RNA pol II transcription sites overlap enhancers. PLoS Biol. 2010; 8(5):e1000384. PMC: 2867938. DOI: 10.1371/journal.pbio.1000384. View

Kablar B, Krastel K, Ying C, Tapscott S, Goldhamer D, Rudnicki M . Myogenic determination occurs independently in somites and limb buds. Dev Biol. 1999; 206(2):219-31. DOI: 10.1006/dbio.1998.9126. View

Maston G, Evans S, Green M . Transcriptional regulatory elements in the human genome. Annu Rev Genomics Hum Genet. 2006; 7:29-59. DOI: 10.1146/annurev.genom.7.080505.115623. View

Mousavi K, Zare H, Wang A, Sartorelli V . Polycomb protein Ezh1 promotes RNA polymerase II elongation. Mol Cell. 2011; 45(2):255-62. DOI: 10.1016/j.molcel.2011.11.019. View

Kornberg R, Lorch Y . Chromatin structure and transcription. Annu Rev Cell Biol. 1992; 8:563-87. DOI: 10.1146/annurev.cb.08.110192.003023. View

10.

Sanyal A, Lajoie B, Jain G, Dekker J . The long-range interaction landscape of gene promoters. Nature. 2012; 489(7414):109-13. PMC: 3555147. DOI: 10.1038/nature11279. View

11.

Narlikar G, Fan H, Kingston R . Cooperation between complexes that regulate chromatin structure and transcription. Cell. 2002; 108(4):475-87. DOI: 10.1016/s0092-8674(02)00654-2. View

12.

Melo C, Drost J, Wijchers P, van de Werken H, de Wit E, Vrielink J . eRNAs are required for p53-dependent enhancer activity and gene transcription. Mol Cell. 2013; 49(3):524-35. DOI: 10.1016/j.molcel.2012.11.021. View

13.

Orom U, Shiekhattar R . Noncoding RNAs and enhancers: complications of a long-distance relationship. Trends Genet. 2011; 27(10):433-9. PMC: 4484734. DOI: 10.1016/j.tig.2011.06.009. View

14.

Bulger M, Groudine M . Functional and mechanistic diversity of distal transcription enhancers. Cell. 2011; 144(3):327-39. PMC: 3742076. DOI: 10.1016/j.cell.2011.01.024. View

15.

Blais A, Tsikitis M, Acosta-Alvear D, Sharan R, Kluger Y, Dynlacht B . An initial blueprint for myogenic differentiation. Genes Dev. 2005; 19(5):553-69. PMC: 551576. DOI: 10.1101/gad.1281105. View

16.

Hah N, Murakami S, Nagari A, Danko C, Kraus W . Enhancer transcripts mark active estrogen receptor binding sites. Genome Res. 2013; 23(8):1210-23. PMC: 3730096. DOI: 10.1101/gr.152306.112. View

17.

Creyghton M, Cheng A, Welstead G, Kooistra T, Carey B, Steine E . Histone H3K27ac separates active from poised enhancers and predicts developmental state. Proc Natl Acad Sci U S A. 2010; 107(50):21931-6. PMC: 3003124. DOI: 10.1073/pnas.1016071107. View

18.

Trapnell C, Williams B, Pertea G, Mortazavi A, Kwan G, van Baren M . Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation. Nat Biotechnol. 2010; 28(5):511-5. PMC: 3146043. DOI: 10.1038/nbt.1621. View

19.

Paranjape S, Kamakaka R, Kadonaga J . Role of chromatin structure in the regulation of transcription by RNA polymerase II. Annu Rev Biochem. 1994; 63:265-97. DOI: 10.1146/annurev.bi.63.070194.001405. View

20.

Orom U, Derrien T, Beringer M, Gumireddy K, Gardini A, Bussotti G . Long noncoding RNAs with enhancer-like function in human cells. Cell. 2010; 143(1):46-58. PMC: 4108080. DOI: 10.1016/j.cell.2010.09.001. View