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Clinical Reviews in Allergy & Immunology

, Volume 39, Issue 1, pp 20–29 | Cite as

X Chromosome Inactivation and Autoimmunity

  • Wesley H. BrooksEmail author
Article

Abstract

Autoimmune diseases appear to have multiple contributing factors including genetics, epigenetics, environmental factors, and aging. The predominance of females among patients with autoimmune diseases suggests possible involvement of the X chromosome and X chromosome inactivation. X chromosome inactivation is an epigenetic event resulting in multiple levels of control for modulation of the expression of X-linked genes in normal female cells such that there remains only one active X chromosome in the cell. The extent of this control is unique among the chromosomes and has the potential for problems when regulation is disrupted. Here we discuss the X chromosome inactivation process and how the X chromosome and X chromosome inactivation may be involved in development of autoimmune disorders.

Keywords

X chromosome X inactivation Autoimmunity Polyamines 

Abbreviations

dcSAM

Decarboxylated S-adenosylmethionine

EBV

Epstein–Barr virus

LINE

Long interspersed nuclear element

MS

Multiple sclerosis

PAD

Peptidyl arginine deiminase

PAR1, PAR2

Pseudo-autosomal regions of the X chromosome

SAF

Scaffold attachment factor

SAM

S-adenosylmethionine, the cellular methyl group donor

SAMDC

SAM decarboxylase, a key, initial enzyme in polyamine synthesis

SAT1

Spermidine/spermine-N1-acetyltransferase, an enzyme in polyamine recycling

SMS

Spermine synthase, an enzyme in polyamine synthesis

TSIX

An anti-sense gene to the XIST gene, involved in initiation of XCI

Xa

The active X chromosome

XAR

X-added region

XCI

X chromosome inactivation, epigenetic silencing of X chromosomes

XCR

X-conserved region

Xi

The inactive X chromosome

XIC

X-inactivation center, locus of genes involved in initiating XCI

XIST

X-inactivation specific transcript, a key gene in initiating XCI

X-CGD

X-linked chronic granulomatous disease

Xp

X chromosome short arm

Xq

X chromosome long arm

Notes

Acknowledgements

The author would like to thank Dr. Yves Renaudineau (University of Brest, Brest, France) for his kind advice in the preparation of this manuscript. The author would also like to thank Dr. Thomas Yang (University of Florida, Gainesville, Florida, USA) for providing the cell lines and facilities used in preparing Fig. 2. The author would also like to thank Dr. Missag Parseghian (Peregrine Pharmaceuticals, Inc., Tustin, California, USA) for providing the anti-histone H1 antibodies used in Fig. 2.

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Copyright information

© Humana Press Inc. 2009

Authors and Affiliations

  1. 1.Experimental HTS, Drug DiscoveryH. Lee Moffitt Cancer Center & Research InstituteTampaUSA
  2. 2.Drug Discovery, SRB-3H. Lee Moffitt Cancer Center & Research InstituteTampaUSA

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