X inactivation Xplained.

Random inactivation of one of the two female X chromosomes establishes dosage compensation between XY males and XX females in placental mammals. X inactivation is controlled by the X inactivation center (Xic). Recent advances in genome sequencing show that the Xic has evolved from an ancestral vertebrate gene cluster in placental mammals and has undergone separate rearrangements in marsupials. The Xic ensures that all but one X chromosome per diploid genome are inactivated. Which chromosome remains active is randomly chosen. Pairing of Xic loci on the two X chromosomes and alternate states of the X chromosomes before inactivation have recently been implicated in the mechanism of random choice. Chromosome-wide silencing is then initiated by the noncoding Xist RNA, which evolved with the mammalian Xic and covers the inactive X chromosome.

[1]  Thomas Cremer,et al.  Chromosome territories--a functional nuclear landscape. , 2006, Current opinion in cell biology.

[2]  E. Heard,et al.  A novel role for Xist RNA in the formation of a repressive nuclear compartment into which genes are recruited when silenced. , 2006, Genes & development.

[3]  R. Jaenisch,et al.  Loss of methylation activates Xist in somatic but not in embryonic cells. , 1995, Genes & development.

[4]  J. Mcneil,et al.  Word frequency analysis reveals enrichment of dinucleotide repeats on the human X chromosome and [GATA]n in the X escape region. , 2006, Genome research.

[5]  R. Jaenisch,et al.  Hematopoietic Precursor Cells Transiently Reestablish Permissiveness for XInactivation , 2006, Molecular and Cellular Biology.

[6]  Jeannie T. Lee,et al.  A transient heterochromatic state in Xist preempts X inactivation choice without RNA stabilization. , 2006, Molecular cell.

[7]  Chia-Lun Tsai,et al.  Transient Homologous Chromosome Pairing Marks the Onset of X Inactivation , 2006, Science.

[8]  M. Nicodemi,et al.  Symmetry-breaking model for X-chromosome inactivation. , 2007, Physical review letters.

[9]  H. Stunnenberg,et al.  Histone modification patterns associated with the human X chromosome , 2006, EMBO reports.

[10]  T. Jenuwein,et al.  Recruitment of PRC1 function at the initiation of X inactivation independent of PRC2 and silencing , 2006, The EMBO journal.

[11]  H. Willard,et al.  X-inactivation profile reveals extensive variability in X-linked gene expression in females , 2005, Nature.

[12]  A. Chess,et al.  Gene Body-Specific Methylation on the Active X Chromosome , 2007, Science.

[13]  A. Arnold,et al.  Dosage compensation is less effective in birds than in mammals , 2007, Journal of biology.

[14]  A. Bird,et al.  Mbd2 Contributes to DNA Methylation-Directed Repression of the Xist Gene , 2007, Molecular and Cellular Biology.

[15]  P. Avner,et al.  Expression Xist Regulator of ′ a 3 Locus , DXPas 34 Functional Analysis of the , 1999 .

[16]  R. Jaenisch,et al.  Conditional deletion of Xist disrupts histone macroH2A localization but not maintenance of X inactivation , 1999, Nature Genetics.

[17]  M. Kuroda,et al.  Noncoding RNAs and Intranuclear Positioning in Monoallelic Gene Expression , 2007, Cell.

[18]  Cory M. Valley,et al.  Chromosome-wide, allele-specific analysis of the histone code on the human X chromosome. , 2006, Human molecular genetics.

[19]  Laurent Duret,et al.  The Xist RNA Gene Evolved in Eutherians by Pseudogenization of a Protein-Coding Gene , 2006, Science.

[20]  B. Migeon,et al.  Species differences in TSIX/Tsix reveal the roles of these genes in X-chromosome inactivation. , 2002, American journal of human genetics.

[21]  P. Avner,et al.  Methylation profiles of DXPas34 during the onset of X-inactivation. , 2001, Human molecular genetics.

[22]  Huntington F Willard,et al.  Multiple spatially distinct types of facultative heterochromatin on the human inactive X chromosome. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[23]  E. Heard,et al.  RNA and protein actors in X-chromosome inactivation. , 2006, Cold Spring Harbor symposia on quantitative biology.

[24]  Jeannie T. Lee,et al.  Identification of a Ctcf cofactor, Yy1, for the X chromosome binary switch. , 2007, Molecular cell.

[25]  Jeannie T. Lee,et al.  The search for a marsupial XIC reveals a break with vertebrate synteny , 2007, Chromosome Research.

[26]  Richard Axel,et al.  Interchromosomal Interactions and Olfactory Receptor Choice , 2006, Cell.

[27]  M. Wakefield,et al.  The region homologous to the X-chromosome inactivation centre has been disrupted in marsupial and monotreme mammals , 2007, Chromosome Research.

[28]  C. Disteche,et al.  Dosage compensation in mammals: fine-tuning the expression of the X chromosome. , 2006, Genes & development.

[29]  F. Pauler,et al.  Silencing by imprinted noncoding RNAs: is transcription the answer? , 2007, Trends in genetics : TIG.

[30]  J. Mcneil,et al.  The X chromosome is organized into a gene-rich outer rim and an internal core containing silenced nongenic sequences , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[31]  N. Xu,et al.  X-chromosome kiss and tell: how the Xs go their separate ways. , 2006, Cold Spring Harbor symposia on quantitative biology.

[32]  N. Brockdorff,et al.  Attenuated spread of X-inactivation in an X;autosome translocation , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[33]  Jeannie T. Lee.  Homozygous Tsix mutant mice reveal a sex-ratio distortion and revert to random X-inactivation , 2002, Nature Genetics.

[34]  David L. Steffen,et al.  The DNA sequence of the human X chromosome , 2005, Nature.

[35]  G. H. Jacobs,et al.  Response to Comment on "Emergence of Novel Color Vision in Mice Engineered to Express a Human Cone Photopigment" , 2007, Science.

[36]  Roland Eils,et al.  Transient colocalization of X-inactivation centres accompanies the initiation of X inactivation , 2006, Nature Cell Biology.

[37]  Rudolf Jaenisch,et al.  Chromosomal silencing and localization are mediated by different domains of Xist RNA , 2002, Nature Genetics.

[38]  M. Busslinger,et al.  Pax5 induces V-to-DJ rearrangements and locus contraction of the immunoglobulin heavy-chain gene. , 2004, Genes & development.

[39]  J. Sedat,et al.  The Mcp element mediates stable long-range chromosome-chromosome interactions in Drosophila. , 2006, Molecular biology of the cell.

[40]  Y. Hoki,et al.  Tsix defective in splicing is competent to establish Xist silencing , 2006, Development.

[41]  Anton Wutz,et al.  A Chromosomal Memory Triggered by Xist Regulates Histone Methylation in X Inactivation , 2004, PLoS biology.

[42]  M. Sasaki,et al.  Preferential inactivation of the paternally derived X chromosome in the extraembryonic membranes of the mouse , 1975, Nature.

[43]  A. Farazmand,et al.  Expression of XIST sense and antisense in bovine fetal organs and cell cultures , 2004, Chromosome Research.

[44]  N. Brockdorff,et al.  Global hypomethylation of the genome in XX embryonic stem cells , 2005, Nature Genetics.

[45]  M. Lyon.  The Lyon and the LINE hypothesis. , 2003, Seminars in cell & developmental biology.

[46]  Jeannie T. Lee,et al.  Perinucleolar Targeting of the Inactive X during S Phase: Evidence for a Role in the Maintenance of Silencing , 2007, Cell.

[47]  W. G. Kelly,et al.  Chromatin remodeling in dosage compensation. , 2005, Annual review of genetics.

[48]  S. Whitehead,et al.  Genes flanking Xist in mouse and human are separated on the X chromosome in American marsupials , 2007, Chromosome Research.

[49]  Jennifer A. Erwin,et al.  The DXPas34 repeat regulates random and imprinted X inactivation. , 2007, Developmental cell.

[50]  Susanna Mlynarczyk-Evans,et al.  X Chromosomes Alternate between Two States prior to Random X-Inactivation , 2006, PLoS biology.

[51]  B. Turner,et al.  Defining an epigenetic code , 2007, Nature Cell Biology.

[52]  Christine M Disteche,et al.  Dosage compensation of the active X chromosome in mammals , 2006, Nature Genetics.

[53]  P. Avner,et al.  An essential role for the DXPas34 tandem repeat and Tsix transcription in the counting process of X chromosome inactivation. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[54]  L. Carrel,et al.  Genomic Environment Predicts Expression Patterns on the Human Inactive X Chromosome , 2006, PLoS genetics.