Allele-specific Repression of Sox2 Through the Long Non-coding RNA Sox2ot

Overview

Journal Sci Rep

Specialty Science

Date 2018 Jan 12

PMID 29321583

Citations 14

Authors

Tobias C Messemaker

Selina M van Leeuwen

Patrick R van den Berg

Anke E J t Jong

Robert-Jan Palstra

Rob C Hoeben

Stefan Semrau

Harald M M Mikkers

Affiliations

Soon will be listed here.

Abstract

The transcription factor Sox2 controls the fate of pluripotent stem cells and neural stem cells. This gatekeeper function requires well-regulated Sox2 levels. We postulated that Sox2 regulation is partially controlled by the Sox2 overlapping long non-coding RNA (lncRNA) gene Sox2ot. Here we show that the RNA levels of Sox2ot and Sox2 are inversely correlated during neural differentiation of mouse embryonic stem cells (ESCs). Through allele-specific enhanced transcription of Sox2ot in mouse Sox2eGFP knockin ESCs we demonstrate that increased Sox2ot transcriptional activity reduces Sox2 RNA levels in an allele-specific manner. Enhanced Sox2ot transcription, yielding lower Sox2 RNA levels, correlates with a decreased chromatin interaction of the upstream regulatory sequence of Sox2 and the ESC-specific Sox2 super enhancer. Our study indicates that, in addition to previously reported in trans mechanisms, Sox2ot can regulate Sox2 by an allele-specific mechanism, in particular during development.

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References

Askarian-Amiri M, Seyfoddin V, Smart C, Wang J, Kim J, Hansji H . Emerging role of long non-coding RNA SOX2OT in SOX2 regulation in breast cancer. PLoS One. 2014; 9(7):e102140. PMC: 4090206. DOI: 10.1371/journal.pone.0102140. View

Wood H, Episkopou V . Comparative expression of the mouse Sox1, Sox2 and Sox3 genes from pre-gastrulation to early somite stages. Mech Dev. 1999; 86(1-2):197-201. DOI: 10.1016/s0925-4773(99)00116-1. View

Semrau S, Crosetto N, Bienko M, Boni M, Bernasconi P, Chiarle R . FuseFISH: robust detection of transcribed gene fusions in single cells. Cell Rep. 2013; 6(1):18-23. PMC: 4214547. DOI: 10.1016/j.celrep.2013.12.002. View

Tosetti V, Sassone J, Ferri A, Taiana M, Bedini G, Nava S . Transcriptional role of androgen receptor in the expression of long non-coding RNA Sox2OT in neurogenesis. PLoS One. 2017; 12(7):e0180579. PMC: 5507538. DOI: 10.1371/journal.pone.0180579. View

Brockdorff N . Noncoding RNA and Polycomb recruitment. RNA. 2013; 19(4):429-42. PMC: 3677253. DOI: 10.1261/rna.037598.112. View

Kang W, Hebert J . A Sox2 BAC transgenic approach for targeting adult neural stem cells. PLoS One. 2012; 7(11):e49038. PMC: 3492187. DOI: 10.1371/journal.pone.0049038. View

Cai N, Li M, Qu J, Liu G, Izpisua Belmonte J . Post-translational modulation of pluripotency. J Mol Cell Biol. 2012; 4(4):262-5. DOI: 10.1093/jmcb/mjs031. View

Avilion A, Nicolis S, Pevny L, Perez L, Vivian N, Lovell-Badge R . Multipotent cell lineages in early mouse development depend on SOX2 function. Genes Dev. 2003; 17(1):126-40. PMC: 195970. DOI: 10.1101/gad.224503. View

Wang K, Yang Y, Liu B, Sanyal A, Corces-Zimmerman R, Chen Y . A long noncoding RNA maintains active chromatin to coordinate homeotic gene expression. Nature. 2011; 472(7341):120-4. PMC: 3670758. DOI: 10.1038/nature09819. View

10.

Crevillen P, Sonmez C, Wu Z, Dean C . A gene loop containing the floral repressor FLC is disrupted in the early phase of vernalization. EMBO J. 2012; 32(1):140-8. PMC: 3545306. DOI: 10.1038/emboj.2012.324. View

11.

Shahryari A, Rafiee M, Fouani Y, Oliae N, Mansour Samaei N, Shafiee M . Two novel splice variants of SOX2OT, SOX2OT-S1, and SOX2OT-S2 are coupregulated with SOX2 and OCT4 in esophageal squamous cell carcinoma. Stem Cells. 2013; 32(1):126-34. DOI: 10.1002/stem.1542. View

12.

Lee T, Young R . Transcriptional regulation and its misregulation in disease. Cell. 2013; 152(6):1237-51. PMC: 3640494. DOI: 10.1016/j.cell.2013.02.014. View

13.

Chodroff R, Goodstadt L, Sirey T, Oliver P, Davies K, Green E . Long noncoding RNA genes: conservation of sequence and brain expression among diverse amniotes. Genome Biol. 2010; 11(7):R72. PMC: 2926783. DOI: 10.1186/gb-2010-11-7-r72. View

14.

Carninci P, Hayashizaki Y . Noncoding RNA transcription beyond annotated genes. Curr Opin Genet Dev. 2007; 17(2):139-44. DOI: 10.1016/j.gde.2007.02.008. View

15.

Masui S, Nakatake Y, Toyooka Y, Shimosato D, Yagi R, Takahashi K . Pluripotency governed by Sox2 via regulation of Oct3/4 expression in mouse embryonic stem cells. Nat Cell Biol. 2007; 9(6):625-35. DOI: 10.1038/ncb1589. View

16.

Nichols J, Smith A . Pluripotency in the embryo and in culture. Cold Spring Harb Perspect Biol. 2012; 4(8):a008128. PMC: 3405859. DOI: 10.1101/cshperspect.a008128. View

17.

Stadhouders R, Kolovos P, Brouwer R, Zuin J, van den Heuvel A, Kockx C . Multiplexed chromosome conformation capture sequencing for rapid genome-scale high-resolution detection of long-range chromatin interactions. Nat Protoc. 2013; 8(3):509-24. DOI: 10.1038/nprot.2013.018. View

18.

Kamachi Y, Kondoh H . Sox proteins: regulators of cell fate specification and differentiation. Development. 2013; 140(20):4129-44. DOI: 10.1242/dev.091793. View

19.

Li Y, Rivera C, Ishii H, Jin F, Selvaraj S, Lee A . CRISPR reveals a distal super-enhancer required for Sox2 expression in mouse embryonic stem cells. PLoS One. 2014; 9(12):e114485. PMC: 4259346. DOI: 10.1371/journal.pone.0114485. View

20.

Bernstein B, Mikkelsen T, Xie X, Kamal M, Huebert D, Cuff J . A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell. 2006; 125(2):315-26. DOI: 10.1016/j.cell.2006.02.041. View