The X Chromosome in Space

Overview

Journal Nat Rev Genet

Specialty Genetics

Date 2017 May 9

PMID 28479596

Citations 81

Authors

Teddy Jegu

Eric Aeby

Jeannie T Lee

Affiliations

Soon will be listed here.

Abstract

Extensive 3D folding is required to package a genome into the tiny nuclear space, and this packaging must be compatible with proper gene expression. Thus, in the well-hierarchized nucleus, chromosomes occupy discrete territories and adopt specific 3D organizational structures that facilitate interactions between regulatory elements for gene expression. The mammalian X chromosome exemplifies this structure-function relationship. Recent studies have shown that, upon X-chromosome inactivation, active and inactive X chromosomes localize to different subnuclear positions and adopt distinct chromosomal architectures that reflect their activity states. Here, we review the roles of long non-coding RNAs, chromosomal organizational structures and the subnuclear localization of chromosomes as they relate to X-linked gene expression.

Citing Articles

Sex chromosomes and gonads modify microglial-mediated pathology in a mouse model of Alzheimer's disease.

Casali B, Lin L, Benedict O, Zuppe H, Marsico E, Reed E J Neuroinflammation. 2025; 22(1):81.

PMID: 40083008 PMC: 11907917. DOI: 10.1186/s12974-025-03404-8.

Aging activates escape of the silent X chromosome in the female mouse hippocampus.

Gadek M, Shaw C, Abdulai-Saiku S, Saloner R, Marino F, Wang D Sci Adv. 2025; 11(10):eads8169.

PMID: 40043106 PMC: 11881916. DOI: 10.1126/sciadv.ads8169.

Visualization of chromosomal reorganization induced by heterologous fusions in the mammalian nucleus.

Yan M, Zhang X, Yang Z, Jia M, Liao R, Li J Nat Commun. 2025; 16(1):1485.

PMID: 39929797 PMC: 11811026. DOI: 10.1038/s41467-024-55582-3.

Non-replicative herpes simplex virus genomic and amplicon vectors for gene therapy - an update.

Le Hars M, Joussain C, Jegu T, Epstein A Gene Ther. 2024; .

PMID: 39533042 DOI: 10.1038/s41434-024-00500-x.

Multifaceted role of CTCF in X-chromosome inactivation.

Bammidi L, Gayen S Chromosoma. 2024; 133(4):217-231.

PMID: 39433641 DOI: 10.1007/s00412-024-00826-w.

References

Riggs A . X inactivation, differentiation, and DNA methylation. Cytogenet Cell Genet. 1975; 14(1):9-25. DOI: 10.1159/000130315. View

Lee J . Homozygous Tsix mutant mice reveal a sex-ratio distortion and revert to random X-inactivation. Nat Genet. 2002; 32(1):195-200. DOI: 10.1038/ng939. View

Kelsey A, Yang C, Leung D, Minks J, Dixon-McDougall T, Baldry S . Impact of flanking chromosomal sequences on localization and silencing by the human non-coding RNA XIST. Genome Biol. 2015; 16:208. PMC: 4591629. DOI: 10.1186/s13059-015-0774-2. View

Yang F, Babak T, Shendure J, Disteche C . Global survey of escape from X inactivation by RNA-sequencing in mouse. Genome Res. 2010; 20(5):614-22. PMC: 2860163. DOI: 10.1101/gr.103200.109. View

Shin J, Wallingford M, Gallant J, Marcho C, Jiao B, Byron M . RLIM is dispensable for X-chromosome inactivation in the mouse embryonic epiblast. Nature. 2014; 511(7507):86-9. PMC: 4105192. DOI: 10.1038/nature13286. View

Yusufzai T, Tagami H, Nakatani Y, Felsenfeld G . CTCF tethers an insulator to subnuclear sites, suggesting shared insulator mechanisms across species. Mol Cell. 2004; 13(2):291-8. DOI: 10.1016/s1097-2765(04)00029-2. View

Ogawa Y, Lee J . Xite, X-inactivation intergenic transcription elements that regulate the probability of choice. Mol Cell. 2003; 11(3):731-43. DOI: 10.1016/s1097-2765(03)00063-7. View

Sado T, Wang Z, Sasaki H, Li E . Regulation of imprinted X-chromosome inactivation in mice by Tsix. Development. 2001; 128(8):1275-86. DOI: 10.1242/dev.128.8.1275. View

Dietzel S, Schiebel K, Little G, Edelmann P, Rappold G, Eils R . The 3D positioning of ANT2 and ANT3 genes within female X chromosome territories correlates with gene activity. Exp Cell Res. 1999; 252(2):363-75. DOI: 10.1006/excr.1999.4635. View

10.

Lieberman-Aiden E, van Berkum N, Williams L, Imakaev M, Ragoczy T, Telling A . Comprehensive mapping of long-range interactions reveals folding principles of the human genome. Science. 2009; 326(5950):289-93. PMC: 2858594. DOI: 10.1126/science.1181369. View

11.

Zorca C, Kim L, Kim Y, Krause M, Zenklusen D, Spilianakis C . Myosin VI regulates gene pairing and transcriptional pause release in T cells. Proc Natl Acad Sci U S A. 2015; 112(13):E1587-93. PMC: 4386387. DOI: 10.1073/pnas.1502461112. View

12.

Hall L, Byron M, Sakai K, Carrel L, Willard H, Lawrence J . An ectopic human XIST gene can induce chromosome inactivation in postdifferentiation human HT-1080 cells. Proc Natl Acad Sci U S A. 2002; 99(13):8677-82. PMC: 124357. DOI: 10.1073/pnas.132468999. View

13.

Dyer K, Canfield T, Gartler S . Molecular cytological differentiation of active from inactive X domains in interphase: implications for X chromosome inactivation. Cytogenet Cell Genet. 1989; 50(2-3):116-20. DOI: 10.1159/000132736. View

14.

Lee J, Strauss W, Dausman J, Jaenisch R . A 450 kb transgene displays properties of the mammalian X-inactivation center. Cell. 1996; 86(1):83-94. DOI: 10.1016/s0092-8674(00)80079-3. View

15.

Clemson C, McNeil J, Willard H, Lawrence J . XIST RNA paints the inactive X chromosome at interphase: evidence for a novel RNA involved in nuclear/chromosome structure. J Cell Biol. 1996; 132(3):259-75. PMC: 2120729. DOI: 10.1083/jcb.132.3.259. View

16.

Tsai C, Rowntree R, Cohen D, Lee J . Higher order chromatin structure at the X-inactivation center via looping DNA. Dev Biol. 2008; 319(2):416-25. PMC: 2567126. DOI: 10.1016/j.ydbio.2008.04.010. View

17.

Monkhorst K, Jonkers I, Rentmeester E, Grosveld F, Gribnau J . X inactivation counting and choice is a stochastic process: evidence for involvement of an X-linked activator. Cell. 2008; 132(3):410-21. DOI: 10.1016/j.cell.2007.12.036. View

18.

Engreitz J, Pandya-Jones A, McDonel P, Shishkin A, Sirokman K, Surka C . The Xist lncRNA exploits three-dimensional genome architecture to spread across the X chromosome. Science. 2013; 341(6147):1237973. PMC: 3778663. DOI: 10.1126/science.1237973. View

19.

Bourgeois C, Laquerriere F, Hemon D, Hubert J, BOUTEILLE M . New data on the in-situ position of the inactive X chromosome in the interphase nucleus of human fibroblasts. Hum Genet. 1985; 69(2):122-9. DOI: 10.1007/BF00293281. View

20.

Barakat T, Loos F, van Staveren S, Myronova E, Ghazvini M, Grootegoed J . The trans-activator RNF12 and cis-acting elements effectuate X chromosome inactivation independent of X-pairing. Mol Cell. 2014; 53(6):965-78. DOI: 10.1016/j.molcel.2014.02.006. View