Dosage compensation of the sex chromosomes

Annual Review of Genetics

Volumn 46, Issue , 2012, Pages 537-560

  Disteche, Christine M ^a  

^a UNIVERSITY OF WASHINGTON   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANEUPLOIDY; BIRD; CAENORHABDITIS ELEGANS; CHROMOSOME NUMBER; DISEASE PREDISPOSITION; DROSOPHILA; DROSOPHILA MELANOGASTER; GENE DOSAGE; GENE EXPRESSION REGULATION; GENE INACTIVATION; GENE REPRESSION; GENE SILENCING; GENETIC CONSERVATION; HAPLOINSUFFICIENCY; MARSUPIAL; MOLECULAR GENETICS; MONOSOMY; MONOTREMATE; NEMATODE; NONHUMAN; POLYPLOIDY; POLYSOMY; PRIORITY JOURNAL; REPRODUCTION; REVIEW; SEX CHROMOSOME; UPREGULATION;

ALLELES; ANEUPLOIDY; ANIMALS; BIRDS; DOSAGE COMPENSATION, GENETIC; DROSOPHILA; EVOLUTION, MOLECULAR; FEMALE; GENETIC VARIATION; MALE; MAMMALS; NEMATODA; POLYPLOIDY; RNA, UNTRANSLATED; SEX FACTORS; X CHROMOSOME; Y CHROMOSOME;

AVES; MAMMALIA; NEMATODA;

EID: 84870174108     PISSN: 00664197     EISSN: 15452948     Source Type: Book Series    
DOI: 10.1146/annurev-genet-110711-155454     Document Type: Review

References (178)

1. Adler DA, Rugarli EI, Lingenfelter PA, Tsuchiya K, Poslinski D, et al. 1997. Evidence of evolutionary up-regulation of the single active X chromosome in mammals based on Clc4 expression levels in Mus spretus and Mus musculus. Proc. Natl. Acad. Sci. USA 94:9244-48
2. Agrelo R, Souabni A, Novatchkova M, Haslinger C, Leeb M, et al. 2009. SATB1 defines the developmental context for gene silencing by Xist in lymphoma and embryonic cells. Dev. Cell 16:507-16
3. Al Nadaf S, Deakin JE, Gilbert C, Robinson TJ, Graves JA, Waters PD. 2011. A cross-species comparison of escape from X inactivation in Eutheria: implications for evolution of X chromosome inactivation. Chromosoma 121:71-78
4. Al Nadaf S, Waters PD, Koina E, Deakin JE, Jordan KS, Graves JA. 2010. Activity map of the tammar X chromosome shows that marsupial X inactivation is incomplete and escape is stochastic. Genome Biol. 11:R122
5. Andina RJ. 1978. A study of X chromosome regulation during oogenesis in the mouse. Exp. Cell Res. 111:211-18
6. Arnold AP. 2011. The end of gonad-centric sex determination in mammals. Trends Genet. 28:55-61
7. Bachtrog D, Kirkpatrick M, Mank JE, McDaniel SF, Pires JC, et al. 2011. Are all sex chromosomes created equal? Trends Genet. 27:350-57
8. Barr ML, Bertram EG. 1949. A morphological distinction between neurones of the male and female, and the behaviour of the nucleolar satellite during accelerated nucleoprotein synthesis. Nature 163:676
9. Bartolomei MS, Ferguson-Smith AC. 2011. Mammalian genomic imprinting. Cold Spring Harb. Perspect. Biol. 3:a002592
10. Bellott DW, Skaletsky H, Pyntikova T, Mardis ER, Graves T, et al. 2010. Convergent evolution of chicken Z and human X chromosomes by expansion and gene acquisition. Nature 466:612-16
11. Berletch JB, Yang F, Xu J, Carrel L, Disteche CM. 2011. Genes that escape from X inactivation. Hum. Genet. 130:237-45
12. Bernardo Carvalho A, Koerich LB, Clark AG. 2009. Origin and evolution of Y chromosomes: Drosophila tales. Trends Genet. 25:270-77
13. Bhadra MP, Bhadra U, Kundu J, Birchler JA. 2005. Gene expression analysis of the function of the male-specific lethal complex in Drosophila. Genetics 169:2061-74
14. Birchler J, Sun L, Fernandez H, Donohue R, Xie W, Sanyal A. 2011. Re-evaluation of the function of the male specific lethal complex in Drosophila. J. Genet. Genomics 38:327-32
15. Birchler JA. 2010. Reflections on studies of gene expression in aneuploids. Biochem. J. 426:119-23
16. Birchler JA, Fernandez HR, Kavi HH. 2006. Commonalities in compensation. BioEssays 28:565-68
17. Birchler JA, Veitia RA. 2007. The gene balance hypothesis: from classical genetics to modern genomics. Plant Cell 19:395-402
18. Bix M, Locksley RM. 1998. Independent and epigenetic regulation of the interleukin-4 alleles in CD4+ T cells. Science 281:1352-54
19. Bollenbach T, Kishony R. 2009. Quiet gene circuit more fragile than its noisy peer. Cell 139:460-61
20. Brawand D, Soumillon M, Necsulea A, Julien P, Csárdi G, et al. 2011. The evolution of gene expression levels in mammalian organs. Nature 478:343-48
21. Brown CJ, Greally JM. 2003. A stain upon the silence: genes escaping X inactivation. Trends Genet. 19:432-38
22. Burga A, Casanueva MO, Lehner B. 2011. Predicting mutation outcome from early stochastic variation in genetic interaction partners. Nature 480:250-53
23. Cantrell MA, Carstens BC, Wichman HA. 2009. X chromosome inactivation and Xist evolution in a rodent lacking LINE-1 activity. PLoS One 4:e6252
24. Carrel L, Willard HF. 2005. X-inactivation profile reveals extensive variability in X-linked gene expression in females. Nature 434:400-4
25. Charlesworth B. 1991. The evolution of sex chromosomes. Science 251:1030-33
26. Chaumeil J, Le Baccon P, Wutz A, Heard E. 2006. A novel role for Xist RNA in the formation of a repressive nuclear compartment into which genes are recruited when silenced. Genes Dev. 20:2223-37
27. Cheng Z, Ventura M, She X, Khaitovich P, Graves T, et al. 2005. A genome-wide comparison of recent chimpanzee and human segmental duplications. Nature 437:88-93
28. Chow JC, Heard E. 2010. Nuclear organization and dosage compensation. Cold Spring Harb. Perspect. Biol. 2(11):a000604
29. Chu C, Qu K, Zhong FL, Artandi SE, Chang HY. 2011. Genomic maps of long noncoding RNA occupancy reveal principles of RNA-chromatin interactions. Mol. Cell 44:667-78
30. Cline TW, Meyer BJ. 1996. Vive la difference: males versus females in flies versus worms. Annu. Rev. Genet. 30:637-702
31. Conrad T, Akhtar A. 2012. Dosage compensation in Drosophila melanogaster: epigenetic fine-tuning of chromosome-wide transcription. Nat. Rev. Genet. 13:123-34
32. Conrad T, Cavalli FM, Vaquerizas JM, Luscombe NM, Akhtar A. 2012. Drosophila dosage compensation involves enhanced Pol II recruitment to male X-linked promoters. Science 337:742-46
33. Cooper GM, Nickerson DA, Eichler EE. 2007. Mutational and selective effects on copy-number variants in the human genome. Nat. Genet. 39:S22-29
34. Csankovszki G, McDonel P, Meyer BJ. 2004. Recruitment and spreading of the C. elegans dosage compensation complex along X chromosomes. Science 303:1182-85
35. D'EspositoM, Ciccodicola A, Gianfrancesco F, EspositoT, Flagiello L, et al. 1996.Asynaptobrevin-like gene in the Xq28 pseudoautosomal region undergoes X inactivation. Nat. Genet. 13:227-29
36. de ClareM, Pir P, Oliver SG. 2011. Haploinsufficiency and the sex chromosomes from yeasts to humans. BMC Biol. 9:15
37. Deakin JE, Hore TA, Koina E, Marshall Graves JA. 2008. The status of dosage compensation in the multiple X chromosomes of the platypus. PLoS Genet 4: e1000140
38. Demuth JP, Hahn MW. 2009. The life and death of gene families. BioEssays 31:29-39
39. Deng X, Hiatt JB, Nguyen DK, Ercan S, Sturgill D, et al. 2011. Evidence for compensatory upregulation of expressed X-linked genes in mammals, Caenorhabditis elegans and Drosophila melanogaster. Nat. Genet. 43:1179-85
40. Deng X, Nguyen DK, Hansen RS, Van Dyke DL, Gartler SM, Disteche CM. 2009. Dosage regulation of the active X chromosome in human triploid cells. PLoS Genet. 5:e1000751
41. Disteche CM, Filippova GN, Tsuchiya KD. 2002. Escape from X inactivation. Cytogenet. Genome Res. 99:36-43
42. Duret L, Chureau C, Samain S, Weissenbach J, Avner P. 2006. TheXistRNAgene evolved in eutherians by pseudogenization of a protein-coding gene. Science 312:1653-55
43. Ellis N, Goodfellow PN. 1989. The mammalian pseudoautosomal region. Trends Genet. 5:406-10
44. Epstein CJ. 1986. The Consequences of Chromosome Imbalance. Principles, Mechanisms, and Models. Cambridge, UK: Cambridge Univ. Press
45. Felsenstein J. 1974. The evolutionary advantage of recombination. Genetics 78:737-56
46. FilippovaGN, ChengMK, Moore JM, Truong JP, HuYJ, et al. 2005. Boundaries between chromosomal domains of X inactivation and escape bind CTCF and lack CpGmethylation during early development. Dev. Cell 8:31-42
47. FitzPatrick DR. 2005. Transcriptional consequences of autosomal trisomy: primary gene dosage with complex downstream effects. Trends Genet. 21:249-53
48. Fragouli E, Wells D, Delhanty JD. 2011. Chromosome abnormalities in the human oocyte. Cytogenet. Genome Res. 133:107-18
49. Gartler SM, Riggs AD. 1983. Mammalian X-chromosome inactivation. Annu. Rev. Genet. 17:155-90
50. Gartler SM, Varadarajan KR, Luo P, Norwood TH, Canfield TK, Hansen RS. 2006. Abnormal X: autosome ratio, but normal X chromosome inactivation in human triploid cultures. BMC Genet. 7:41
51. Gelbart ME, Kuroda MI. 2009. Drosophila dosage compensation: a complex voyage to the X chromosome. Development 136:1399-410
52. Gendrel AV, Apedaile A, Coker H, Termanis A, Zvetkova I, et al. 2012. Smchd1-dependent and - independent pathways determine developmental dynamics of CpG island methylation on the inactive X chromosome. Dev. Cell. 23:265-79
53. Gimelbrant A, Hutchinson JN, Thompson BR, Chess A. 2007. Widespread monoallelic expression on human autosomes. Science 318:1136-40
54. Girirajan S, Campbell CD, Eichler EE. 2011. Human copy number variation and complex genetic disease. Annu. Rev. Genet. 45:203-26
55. Girirajan S, Rosenfeld JA, Cooper GM, Antonacci F, Siswara P, et al. 2010. A recurrent 16p12.1 microdeletion supports a two-hit model for severe developmental delay. Nat. Genet. 42:203-9
56. Graves JA. 2006. Sex chromosome specialization and degeneration in mammals. Cell 124:901-14
57. Grant J, Mahadevaiah SK, Khil P, Sangrithi MN, Royo H, et al. 2012. Rsx is a metatherian RNA with Xist-like properties in X-chromosome inactivation. Nature 487:254-58
58. Gupta V, Parisi M, Sturgill D, Nuttall R, Doctolero M, et al. 2006. Global analysis of X-chromosome dosage compensation. J. Biol. 5:3
59. Haldane JBS. 1957. The cost of natural selection. J. Genet. 55:511-24
60. Hamada FN, Park PJ, Gordadze PR, Kuroda MI. 2005. Global regulation of X chromosomal genes by the MSL complex in Drosophila melanogaster. Genes Dev. 19:2289-94
61. Han MV, Demuth JP, McGrath CL, Casola C, Hahn MW. 2009. Adaptive evolution of young gene duplicates in mammals. Genome Res. 19:859-67
62. Heard E, Disteche CM. 2006. Dosage compensation in mammals: fine-tuning the expression of the X chromosome. Genes Dev. 20:1848-67
63. Heard E, Turner J. 2011. Function of the sex chromosomes in mammalian fertility. Cold Spring Harb. Perspect. Biol. 3:a002675
64. Henrichsen CN, Chaignat E, Reymond A. 2009. Copy number variants, diseases and gene expression. Hum. Mol. Genet. 18:R1-8
65. Henrichsen CN, Vinckenbosch N, Zollner S, Chaignat E, Pradervand S, et al. 2009. Segmental copy number variation shapes tissue transcriptomes. Nat. Genet. 41:424-29
66. Hughes JF, Skaletsky H, Pyntikova T, Graves TA, van Daalen SK, et al. 2012. Chimpanzee and human Y chromosomes are remarkably divergent in structure and gene content. Nature 463:536-39
67. Huh D, Paulsson J. 2010. Non-genetic heterogeneity from stochastic partitioning at cell division. Nat. Genet. 43:95-100
68. Islam S, Kjallquist U, Moliner A, Zajac P, Fan JB, et al. 2011. Characterization of the single-cell transcriptional landscape by highly multiplex RNA-seq. Genome Res. 21:1160-67
69. Itoh Y, Replogle K, Kim YH, Wade J, ClaytonDF, Arnold AP. 2010. Sex bias and dosage compensation in the zebra finch versus chicken genomes: general and specialized patterns among birds. Genome Res. 20:512-18
70. Jablonka E. 2004. The evolution of the peculiarities of mammalian sex chromosomes: an epigenetic view. BioEssays 26:1327-32
71. Jacobs PA, Szulman AE, Funkhouser J, Matsuura JS, Wilson CC. 1982. Human triploidy: relationship between parental origin of the additional haploid complement and development of partial hydatidiform mole. Ann. Hum. Genet. 46:223-31
72. Jeon Y, Lee JT. 2011. YY1 tethers Xist RNA to the inactive X nucleation center. Cell 146:119-33
73. Johnston CM, Lovell FL, Leongamornlert DA, Stranger BE, Dermitzakis ET, RossMT. 2008. Largescale population study of human cell lines indicates that dosage compensation is virtually complete. PLoS Genet. 4:e9
74. Jonkers I, Barakat TS, Achame EM, Monkhorst K, Kenter A, et al. 2009. RNF12 is an X-encoded dose-dependent activator of X chromosome inactivation. Cell 139:999-1011
75. Julien P, Brawand D, Soumillon M, Necsulea A, Liechti A, et al. 2012. Mechanisms and evolutionary patterns of mammalian and avian dosage compensation. PLoS Biol. 10: e1001328
76. Khaitovich P, Hellmann I, Enard W, Nowick K, LeinweberM, et al. 2005. Parallel patterns of evolution in the genomes and transcriptomes of humans and chimpanzees. Science 309:1850-54
77. Kharchenko PV, Xi R, Park PJ. 2011. Evidence for dosage compensation between the X chromosome and autosomes in mammals. Nat. Genet. 43:1167-69; author reply 71-72
78. Khil PP, Smirnova NA, Romanienko PJ, Camerini-Otero RD. 2004. The mouse X chromosome is enriched for sex-biased genes not subject to selection by meiotic sex chromosome inactivation. Nat. Genet. 36:642-46
79. KimDH, Jeon Y, Anguera MC, Lee JT. 2011. X-chromosome epigenetic reprogramming in pluripotent stem cells via noncoding genes. Semin. Cell Dev. Biol. 22:336-42
80. Kind J, Vaquerizas JM, Gebhardt P, Gentzel M, Luscombe NM, et al. 2008. Genome-wide analysis revealsMOFas a key regulator of dosage compensation and gene expression in Drosophila. Cell 133:813- 28
81. Knight JC. 2004. Allele-specific gene expression uncovered. Trends Genet. 20:113-16
82. Koopman P, Munsterberg A, Capel B, Vivian N, Lovell-Badge R. 1990. Expression of a candidate sex-determining gene during mouse testis differentiation. Nature 348:450-52
83. Kucera KS, Reddy TE, Pauli F, Gertz J, Logan JE, et al. 2011. Allele-specific distribution of RNA polymerase II on female X chromosomes. Hum. Mol. Genet. 20:3964-73
84. Kuroiwa A, Handa S, Nishiyama C, Chiba E, Yamada F, et al. 2011. Additional copies of CBX2 in the genomes of males of mammals lacking SRY, the Amami spiny rat (Tokudaia osimensis) and the Tokunoshima spiny rat (Tokudaia tokunoshimensis). Chromosome Res. 19:635-44
85. Lahn BT, Page DC. 1999. Four evolutionary strata on the human X chromosome. Science 286:877-79
86. Larschan E, Bishop EP, Kharchenko PV, Core LJ, Lis JT, et al. 2011. X chromosome dosage compensation via enhanced transcriptional elongation in Drosophila. Nature 471:115-18
87. Larsson J, Meller VH. 2006. Dosage compensation, the origin and the afterlife of sex chromosomes. Chromosome Res. 14:417-31
88. Leder EH, Cano JM, Leinonen T, O'Hara RB, Nikinmaa M, et al. 2010. Female-biased expression on the X chromosome as a key step in sex chromosome evolution in threespine sticklebacks. Mol. Biol. Evol. 27:1495-503
89. Lee HO, Davidson JM, Duronio RJ. 2009. Endoreplication: polyploidy with purpose. Genes Dev. 23:2461-77
90. Leppig KA, Disteche CM. 2001. Ring X and other structural X chromosome abnormalities: X inactivation and phenotype. Semin. Reprod. Med. 19:147-57
91. Li N, Carrel L. 2008. Escape from X chromosome inactivation is an intrinsic property of the Jarid1c locus. Proc. Natl. Acad. Sci. USA 105:17055-60
92. Lin H, Gupta V, Vermilyea MD, Falciani F, Lee JT, et al. 2007. Dosage compensation in the mouse balances up-regulation and silencing of X-linked genes. PLoS Biol. 5:e326
93. Lin H, Halsall JA, Antczak P, O'Neill LP, Falciani F, Turner BM. 2011. Relative overexpression of X-linked genes in mouse embryonic stem cells is consistent with Ohno's hypothesis. Nat. Genet. 43:1169-70; author reply 71-72
94. Lin F, Xing K, Zhang J, He X. 2012. Expression reduction in mammalian X chromosome evolution refutes Ohno's hypothesis of dosage compensation. Proc. Natl. Acad. Sci. USA 109: 11752-57
95. Lingenfelter PA, Adler DA, PoslinskiD, Thomas S, Elliott RW, et al. 1998. Escape from X inactivation of Smcx is preceded by silencing during mouse development. Nat. Genet. 18:212-13
96. Livernois AM, Graves JA, Waters PD. 2011. The origin and evolution of vertebrate sex chromosomes and dosage compensation. Heredity 108:50-58
97. Lopes AM, Arnold-Croop SE, Amorim A, Carrel L. 2011. Clustered transcripts that escape X inactivation at mouse XqD. Mamm. Genome 22:572-82
98. Lyon MF. 1961. Gene action in the X-chromosome of the mouse (Mus musculus L). Nature 190:372-73
99. Lyon MF. 2003. The Lyon and the LINE hypothesis. Semin. Cell Dev. Biol. 14:313-18
100. Mahadevaiah SK, Royo H, VandeBerg JL, McCarrey JR, Mackay S, Turner JM. 2009. Key features of the X inactivation process are conserved between marsupials and eutherians. Curr. Biol. 19:1478-84
101. Malnic B, Hirono J, Sato T, Buck LB. 1999. Combinatorial receptor codes for odors. Cell 96:713-23
102. Mank JE, Ellegren H. 2009. Sex bias in gene expression is not the same as dosage compensation. Heredity 103:434
103. Mank JE, Hosken DJ, Wedell N. 2011. Some inconvenient truths about sex chromosome dosage compensation and the potential role of sexual conflict. Evolution 65:2133-44
104. Marshall Graves JA. 2002. The rise and fall of SRY. Trends Genet. 18:259-64
105. Masui O, Bonnet I, Le Baccon P, Brito I, Pollex T, et al. 2011. Live-cell chromosome dynamics and outcome of X chromosome pairing events during ES cell differentiation. Cell 145:447-58
106. McDonel P, Jans J, Peterson BK, Meyer BJ. 2006. Clustered DNA motifs mark X chromosomes for repression by a dosage compensation complex. Nature 444:614-18
107. Melamed E, Arnold AP. 2007. Regional differences in dosage compensation on the chicken Z chromosome. Genome Biol. 8:R202
108. Mendjan S, Taipale M, Kind J, Holz H, Gebhardt P, et al. 2006. Nuclear pore components are involved in the transcriptional regulation of dosage compensation in Drosophila. Mol. Cell 21:811-23
109. Meyer BJ. 2010. Targeting X chromosomes for repression. Curr. Opin. Genet. Dev. 20:179-89
110. Migeon BR. 2007. Females Are Mosaic: X Inactivation and Sex Differences in Disease.Oxford: Oxford Univ. Press
111. Mizuno H, Okamoto I, Takagi N. 2002. Developmental abnormalities in mouse embryos tetrasomic for chromosome 11: apparent similarity to embryos functionally disomic for the x chromosome. Genes Genet. Syst. 77:269-76
112. Monkhorst K, Jonkers I, Rentmeester E, Grosveld F, Gribnau J. 2008. X inactivation counting and choice is a stochastic process: evidence for involvement of an X-linked activator. Cell 132:410-21
113. Morey C, Avner P. 2011. The demoiselle of X-inactivation: 50 years old and as trendy and mesmerising as ever. PLoS Genet. 7:e1002212
114. Mueller JL, Mahadevaiah SK, Park PJ, Warburton PE, Page DC, Turner JM. 2008. The mouse X chromosome is enriched formulticopy testis genes showing postmeiotic expression. Nat. Genet. 40:794-99
115. Muller HJ. 1914. A gene for the fourth chromosome of Drosophila. J. Exp. Zool. 17:325-36
116. Muyle A, Zemp N, Deschamps C, Mousset S, Widmer A, Marais GA. 2012. Rapid de novo evolution of X chromosome dosage compensation in Silene latifolia, a plant with young sex chromosomes. PLoS Biol. 10: e1001308
117. Nguyen DK, Disteche CM. 2006. Dosage compensation of the active X chromosome in mammals. Nat. Genet. 38:47-53
118. Nguyen DK, Disteche CM. 2006. High expression of the mammalian X chromosome in brain. Brain Res. 1126:46-49
119. Nguyen DK, Yang F, Kaul R, Alkan C, Antonellis A, et al. 2011. Clcn4-2 genomic structure differs between the X locus in Mus spretus and the autosomal locus in Mus musculus: AT motif enrichment on the X. Genome Res. 21:402-9
120. O'Neill LP, Randall TE, Lavender J, Spotswood HT, Lee JT, Turner BM. 2003. X-linked genes in female embryonic stem cells carry an epigenetic mark prior to the onset of X inactivation. Hum. Mol. Genet. 12:1783-90
121. O'Neill MJ. 2005. The influence of non-coding RNAs on allele-specific gene expression in mammals. Hum. Mol. Genet. 14(Spec. No. 1):R113-20
122. Ohlsson R, Paldi A, Graves JA. 2001. Did genomic imprinting and X chromosome inactivation arise from stochastic expression? Trends Genet. 17:136-41
123. Ohno S. 1967. Sex Chromosomes and Sex Linked Genes. Berlin: Springer-Verlag.
124. Okamoto I, Patrat C, Thepot D, Peynot N, Fauque P, et al. 2011. Eutherian mammals use diverse strategies to initiate X-chromosome inactivation during development. Nature 472:370-74
125. OlsonMV. 1999. When less is more: gene loss as an engine of evolutionary change. Am. J. Hum. Genet. 64:18-23
126. Otto SP. 2007. The evolutionary consequences of polyploidy. Cell 131:452-62
127. Otto SP, Pannell JR, Peichel CL, Ashman TL, Charlesworth D, et al. 2011. About PAR: the distinct evolutionary dynamics of the pseudoautosomal region. Trends Genet. 27:358-67
128. Palmer S, Perry J, Ashworth A. 1995. A contravention of Ohno's law in mice. Nat. Genet. 10:472-76
129. Payer B, Lee JT. 2008. X chromosome dosage compensation: how mammals keep the balance. Annu. Rev. Genet. 42:733-72
130. Peichel CL, Ross JA, Matson CK, DicksonM, Grimwood J, et al. 2004. The master sex-determination locus in threespine sticklebacks is on a nascent Y chromosome. Curr. Biol. 14:1416-24
131. Perry GH, Dominy NJ, Claw KG, Lee AS, Fiegler H, et al. 2007. Diet and the evolution of human amylase gene copy number variation. Nat. Genet. 39:1256-60
132. Pessia E, Makino T, Bailly-Bechet M, McLysaght A, Marais GA. 2012. Mammalian X chromosome inactivation evolved as a dosage-compensation mechanism for dosage-sensitive genes on the X chromosome. Proc. Natl. Acad. Sci. USA 109: 5346-51
133. Quinn AE, Sarre SD, Ezaz T, Marshall Graves JA, Georges A. 2011. Evolutionary transitions between mechanisms of sex determination in vertebrates. Biol. Lett. 7:443-48
134. Raefski AS, O'Neill MJ. 2005. Identification of a cluster of X-linked imprinted genes in mice. Nat. Genet. 37:620-24
135. Raj A, van Oudenaarden A. 2008. Nature, nurture, or chance: stochastic gene expression and its consequences. Cell 135:216-26
136. Reinius B, Shi C, Hengshuo L, Sandhu KS, Radomska KJ, et al. 2010. Female-biased expression of long non-coding RNAs in domains that escape X-inactivation in mouse. BMC Genomics 11:614
137. Rice WR. 1992. Sexually antagonistic genes: experimental evidence. Science 256:1436-39
138. Romito A, Rougeulle C. 2011. Origin and evolution of the long non-coding genes in the X-inactivation center. Biochimie 93:1935-42
139. Ropers HH. 2008. Genetics of intellectual disability. Curr. Opin. Genet. Dev. 18:241-50
140. Ross MT, Grafham DV, Coffey AJ, Scherer S, McLay K, et al. 2005. The DNA sequence of the human X chromosome. Nature 434:325-37
141. Rozen S, Skaletsky H, Marszalek JD, Minx PJ, Cordum HS, et al. 2003. Abundant gene conversion between arms of palindromes in human and ape Y chromosomes. Nature 423:873-76
142. Rugarli EI, Adler DA, BorsaniG, TsuchiyaK, Franco B, et al. 1995. Different chromosomal localization of the Clcn4 gene in Mus spretus and C57BL/6J mice. Nat. Genet. 10:466-71
143. Saran NG, Pletcher MT, Natale JE, Cheng Y, Reeves RH. 2003. Global disruption of the cerebellar transcriptome in a Down syndrome mouse model. Hum. Mol. Genet. 12:2013-19
144. Seidman JG, Seidman C. 2002. Transcription factor haploinsufficiency: when half a loaf is not enough. J. Clin. Invest. 109:451-55
145. Sharp AJ, Spotswood HT, Robinson DO, Turner BM, Jacobs PA. 2002. Molecular and cytogenetic analysis of the spreading of X inactivation in X;autosome translocations. Hum. Mol. Genet. 11:3145-56
146. SimonMD, Wang CI, Kharchenko PV, West JA, Chapman BA, et al. 2011. The genomic binding sites of a noncoding RNA. Proc. Natl. Acad. Sci. USA 108:20497-502
147. Sinclair AH, Berta P, Palmer MS, Hawkins JR, Griffiths BL, et al. 1990. A gene from the human sex-determining region encodes a protein with homology to a conserved DNA-binding motif. Nature 346:240-44
148. Skaletsky H, Kuroda-Kawaguchi T, Minx PJ, Cordum HS, Hillier L, et al. 2003. The male-specific region of the human Y chromosome is a mosaic of discrete sequence classes. Nature 423:825-37
149. Skuse DH. 2005. X-linked genes and mental functioning. Hum. Mol. Genet. 14(Spec. No. 1):R27-32
150. Spatz A, Borg C, Feunteun J. 2004. X-chromosome genetics and human cancer. Nat. Rev. Cancer 4:617-29
151. Splinter E, deWit E, Nora EP, Klous P, van deWerken HJ, et al. 2011. The inactive X chromosome adopts a unique three-dimensional conformation that is dependent on Xist RNA. GenesDev. 25:1371-83
152. Stenberg P, Larsson J. 2011. Buffering and the evolution of chromosome-wide gene regulation. Chromosoma 120:213-25
153. Straub T, Becker PB. 2007. Dosage compensation: the beginning and end of generalization. Nat. Rev. Genet. 8:47-57
154. Sugimoto M, Abe K. 2007. X chromosome reactivation initiates in nascent primordial germ cells in mice. PLoS Genet. 3:e116
155. Turner JM, Mahadevaiah SK, Fernandez-Capetillo O, Nussenzweig A, Xu X, et al. 2005. Silencing of unsynapsed meiotic chromosomes in the mouse. Nat. Genet. 37:41-47
156. Vicoso B, Charlesworth B. 2006. Evolution on the X chromosome: unusual patterns and processes. Nat. Rev. Genet. 7:645-53
157. Wakefield MJ, Keohane AM, Turner BM, Graves JAM. 1997. Histone underacetylation is an ancient component of mammalian X chromosome inactivation. Proc. Natl. Acad. Sci. USA 94:9665-68
158. Wang PJ. 2004. X chromosomes, retrogenes and their role in male reproduction. Trends Endocrinol. Metab. 15:79-83
159. Wang PJ, McCarrey JR, Yang F, Page DC. 2001. An abundance of X-linked genes expressed in spermatogonia. Nat. Genet. 27:422-26
160. Wang Z, Willard HF, Mukherjee S, Furey TS. 2006. Evidence of influence of genomic DNA sequence on human X chromosome inactivation. PLoS Comput. Biol. 2:e113
161. Wareham KA, Lyon MF, Glenister PH, Williams ED. 1987. Age related reactivation of an X-linked gene. Nature 327:725-27
162. Watanabe M, Zinn AR, Page DC, Nishimoto T. 1993. Functional equivalence of human X- and Yencoded isoforms of ribosomal protein S4 consistent with a role in Turner syndrome. Nat. Genet. 4:268-71
163. Wijchers PJ, Yandim C, Panousopoulou E, Ahmad M, Harker N, et al. 2010. Sexual dimorphism in mammalian autosomal gene regulation is determined not only by SRY but by sex chromosome complement as well. Dev. Cell 19:477-84
164. Wilkinson LS, Davies W, Isles AR. 2007. Genomic imprinting effects on brain development and function. Nat. Rev. Neurosci. 8:832-43
165. Wolf JB, Bryk J. 2011. General lack of global dosage compensation in ZZ/ZW systems? Broadening the perspective with RNA-seq. BMC Genomics 12:91
166. Xiong Y, Chen X, Chen Z, Wang X, Shi S, et al. 2010. RNA sequencing shows no dosage compensation of the active X-chromosome. Nat. Genet. 42:1043-47
167. Xu J, Burgoyne PS, Arnold AP. 2002. Sex differences in sex chromosome gene expression in mouse brain. Hum. Mol. Genet. 11:1409-19
168. Xu J, Watkins R, Arnold AP. 2006. Sexually dimorphic expression of the X-linked gene Eif2s3x mRNA but not protein in mouse brain. Gene Expr. Patterns 6:146-55
169. Yang F, Babak T, Shendure J, Disteche CM. 2010. Global survey of escape from X inactivation by RNA-sequencing in mouse. Genome Res. 20:614-22
170. Yang X, Schadt EE, Wang S, Wang H, Arnold AP, et al. 2006. Tissue-specific expression and regulation of sexually dimorphic genes in mice. Genome Res. 16:995-1004
171. Yildirim E, Sadreyev RI, Pinter SF, Lee JT. 2011. X-chromosome hyperactivation in mammals via nonlinear relationships between chromatin states and transcription. Nat. Struct. Mol. Biol. 19:56-61
172. Yin S, DengW, Zheng H, Zhang Z, Hu L, Kong X. 2009. Evidence that the nonsense-mediatedmRNA decay pathway participates in X chromosome dosage compensation in mammals. Biochem. Biophys. Res. Commun. 383:378-82
173. Yin S, WangP, DengW, Zheng H, HuL, et al. 2009. Dosage compensation on the activeXchromosome minimizes transcriptional noise of X-linked genes in mammals. Genome Biol. 10:R74
174. Zechner U, Wilda M, Kehrer-Sawatzki H, Vogel W, Fundele R, Hameister H. 2001. A high density of X-linked genes for general cognitive ability: a run-away process shaping human evolution? Trends Genet. 17:697-701
175. Zhang LF, Huynh KD, Lee JT. 2007. Perinucleolar targeting of the inactive X during S phase: evidence for a role in the maintenance of silencing. Cell 129:693-706
176. Zhang R, Peng Y, Wang W, Su B. 2007. Rapid evolution of an X-linked microRNA cluster in primates. Genome Res. 17:612-17
177. Zhang Y, Malone JH, Powell SK, Periwal V, Spana E, et al. 2010. Expression in aneuploid Drosophila S2 cells. PLoS Biol. 8:e1000320
178. Zvetkova I, Apedaile A, Ramsahoye B, Mermoud JE, CromptonLA, et al. 2005. Global hypomethylation of the genome in XX embryonic stem cells. Nat. Genet. 37:1274-79