Monoallelic expression not due to -regulatory sequence polymorphism poses an intriguing problem in epigenetics because it requires the unequal treatment of two segments of DNA that are present in the same nucleus and that can indeed have absolutely identical sequences. Here, I focus on a few recent developments in the field of monoallelic expression that are of particular interest and raise interesting questions for future work. One development is regarding analyses of imprinted genes, in which recent work suggests the possibility that intriguing networks of imprinted genes exist and are important for genetic and physiological studies. Another issue that has been raised in recent years by a number of publications is the question of how skewed allelic expression should be for it to be designated as monoallelic expression and, further, what methods are appropriate or inappropriate for analyzing genomic data to examine allele-specific expression. Perhaps the most exciting recent development in mammalian monoallelic expression is a clever and carefully executed analysis of genetic diversity of autosomal genes subject to random monoallelic expression (RMAE), which provides compelling evidence for distinct evolutionary forces acting on random monoallelically expressed genes.


Article metrics loading...

Loading full text...

Full text loading...


Literature Cited

  1. Abramowitz LK, Bartolomei MS. 1.  2012. Genomic imprinting: recognition and marking of imprinted loci. Curr. Opin. Genet. Dev. 22:272–78 [Google Scholar]
  2. Adegbola AA, Cox GF, Bradshaw EM, Hafler DA, Gimelbrant A, Chess A. 2.  2015. Monoallelic expression of the human FOXP2 speech gene. PNAS 112:226848–54 [Google Scholar]
  3. Agarwal N, Becker A, Jost KL, Haase S, Thakur BK. 3.  et al. 2011. MeCP2 Rett mutations affect large scale chromatin organization. Hum. Mol. Genet. 20:214187–95 [Google Scholar]
  4. Al Adhami H, Evano B, Le Digarcher A, Gueydan C, Dubois E. 4.  et al. 2015. A systems-level approach to parental genomic imprinting: the imprinted gene network includes extracellular matrix genes and regulates cell cycle exit and differentiation. Genome Res. 25:353–67 [Google Scholar]
  5. Barlow DP, Stoger R, Herrmann BG, Saito K, Schweifer N. 5.  1991. The mouse insulin-like growth factor type-2 receptor is imprinted and closely linked to the Tme locus. Nature 349:84–87 [Google Scholar]
  6. Bartolomei MS, Zemel S, Tilghman SM. 6.  1991. Parental imprinting of the mouse H19 gene. Nature 351:153–55 [Google Scholar]
  7. Bix M, Locksley RM. 7.  1998. Independent and epigenetic regulation of the interleukin-4 alleles in CD4+ T cells. Science 281:53811352–54 [Google Scholar]
  8. Carrel L, Willard HF. 8.  2005. X-inactivation profile reveals extensive variability in X-linked gene expression in females. Nature 434:7031400–4 [Google Scholar]
  9. Cattanach BM, Kirk M. 9.  1985. Differential activity of maternally and paternally derived chromosome regions in mice. Nature 315:6019496–98 [Google Scholar]
  10. Chess A. 10.  2012. Mechanisms and consequences of widespread random monoallelic expression. Nat. Rev. Genet. 13:6421–28 [Google Scholar]
  11. Chess A, Simon I, Cedar H, Axel R. 11.  1994. Allelic inactivation regulates olfactory receptor gene expression. Cell 78:5823–34 [Google Scholar]
  12. Clemson CM, McNeil JA, Willard HF, Lawrence JB. 12.  1996. XIST RNA paints the inactive X chromosome at interphase: evidence for a novel RNA involved in nuclear/chromosome structure. J. Cell Biol. 132:3259–75 [Google Scholar]
  13. Crouse HV. 13.  1960. The controlling element in sex chromosome behavior in sciara. Genetics 45:101429–43 [Google Scholar]
  14. DeChiara TM, Robertson EJ, Efstratiadis A. 14.  1991. Parental imprinting of the mouse insulin-like growth factor II gene. Cell 64:849–59 [Google Scholar]
  15. Degner JF, Marioni JC, Pai AA, Pickrell JK, Nkadori E. 15.  et al. 2009. Effect of read-mapping biases on detecting allele-specific expression from RNA-sequencing data. Bioinformatics 25:243207–12 [Google Scholar]
  16. Deng Q, Ramskold D, Reinius B, Sandberg R. 16.  2014. Single-cell RNA-seq reveals dynamic, random monoallelic gene expression in mammalian cells. Science 343:6167193–96 [Google Scholar]
  17. DeVeale B, van der Kooy D, Babak T. 17.  2012. Critical evaluation of imprinted gene expression by RNA-Seq: a new perspective. PLOS Genet. 8:3e1002600 [Google Scholar]
  18. Donley N, Smith L, Thayer MJ. 18.  2015. ASAR15, a cis-acting locus that controls chromosome-wide replication timing and stability of human chromosome 15. PLOS Genet. 11:1e1004923 [Google Scholar]
  19. Donley N, Stoffregen EP, Smith L, Montagna C, Thayer MJ. 19.  2013. Asynchronous replication, mono-allelic expression, and long range cis-effects of ASAR6. PLOS Genet. 9:4e1003423 [Google Scholar]
  20. Eckersley-Maslin MA, Thybert D, Bergmann JH, Marioni JC, Flicek P, Spector DL. 20.  2014. Random monoallelic gene expression increases upon embryonic stem cell differentiation. Dev. Cell 28:4351–65 [Google Scholar]
  21. Ensminger AW, Chess A. 21.  2004. Coordinated replication timing of monoallelically expressed genes along human autosomes. Hum. Mol. Genet. 13:6651–58 [Google Scholar]
  22. Ferguson-Smith AC. 22.  2011. Genomic imprinting: the emergence of an epigenetic paradigm. Nat. Rev. Genet. 12:8565–75 [Google Scholar]
  23. Gendrel AV, Attia M, Chen CJ, Diabangouaya P, Servant N. 23.  et al. 2014. Developmental dynamics and disease potential of random monoallelic gene expression. Dev. Cell 28:4366–80 [Google Scholar]
  24. Gimelbrant A, Hutchinson JN, Thompson BR, Chess A. 24.  2007. Widespread monoallelic expression on human autosomes. Science 318:58531136–40 [Google Scholar]
  25. Gregg C, Zhang J, Butler JE, Haig D, Dulac C. 25.  2010. Sex-specific parent-of-origin allelic expression in the mouse brain. Science 329:5992682–85 [Google Scholar]
  26. Gregg C, Zhang J, Weissbourd B, Luo S, Schroth GP. 26.  et al. 2010. High-resolution analysis of parent-of-origin allelic expression in the mouse brain. Science 329:5992643–48 [Google Scholar]
  27. Handsaker RE, Van Doren V, Berman JR, Genovese G, Kashin S. 27.  et al. 2015. Large multiallelic copy number variations in humans. Nat. Genet. 47:3296–303 [Google Scholar]
  28. Held W, Roland J, Raulet DH. 28.  1995. Allelic exclusion of Ly49-family genes encoding class I MHC-specific receptors on NK cells. Nature 376:6538355–58 [Google Scholar]
  29. Hellman A, Chess A. 29.  2007. Gene body-specific methylation on the active X chromosome. Science 315:58151141–43 [Google Scholar]
  30. Hollander GA, Zuklys S, Morel C, Mizoguchi E, Mobisson K. 30.  et al. 1998. Monoallelic expression of the interleukin-2 locus. Science 279:53592118–21 [Google Scholar]
  31. Holman L, Kokko H. 31.  2014. The evolution of genomic imprinting: costs, benefits and long-term consequences. Biol. Rev. Camb. Philos. Soc. 89:3568–87 [Google Scholar]
  32. Hozumi N, Tonegawa S. 32.  1976. Evidence for somatic rearrangement of immunoglobulin genes coding for variable and constant regions. PNAS 73:103628–32 [Google Scholar]
  33. Huang HS, Allen JA, Mabb AM, King IF, Miriyala J. 33.  et al. 2012. Topoisomerase inhibitors unsilence the dormant allele of Ube3a in neurons. Nature 481:185–89 [Google Scholar]
  34. Jeffries AR, Collier DA, Vassos E, Curran S, Ogilvie CM, Price J. 34.  2013. Random or stochastic monoallelic expressed genes are enriched for neurodevelopmental disorder candidate genes. PLOS ONE 8:12e85093 [Google Scholar]
  35. Johnson DR. 35.  1974. Hairpin-tail: a case of post-reductional gene action in the mouse egg. Genetics 76:4795–805 [Google Scholar]
  36. Kermicle JL. 36.  1970. Dependence of the R-mottled aleurone phenotype in maize on mode of sexual transmission. Genetics 66:169–85 [Google Scholar]
  37. Lyon MF. 37.  1986. X chromosomes and dosage compensation. Nature 320:6060313 [Google Scholar]
  38. McGrath J, Solter D. 38.  1984. Completion of mouse embryogenesis requires both the maternal and paternal genomes. Cell 37:1179–83 [Google Scholar]
  39. Moore GE, Oakey R. 39.  2011. The role of imprinted genes in humans. Genome Biol. 12:3106 [Google Scholar]
  40. Moore T, Haig D. 40.  1991. Genomic imprinting in mammalian development: a parental tug-of-war. Trends Genet. 7:45–49 [Google Scholar]
  41. Mott R, Yuan W, Kaisaki P, Gan X, Cleak J. 41.  et al. 2014. The architecture of parent-of-origin effects in mice. Cell 156:1–2332–42 [Google Scholar]
  42. Nag A, Savova V, Fung HL, Miron A, Yuan GC. 42.  et al. 2013. Chromatin signature of widespread monoallelic expression. eLife 2:e01256 [Google Scholar]
  43. Nag A, Vigneau S, Savova V, Zwemer LM, Gimelbrant AA. 43.  2015. Chromatin signature identifies monoallelic gene expression across mammalian cell types. G3 Bethesda 5:81713–20 [Google Scholar]
  44. Perez JD, Rubinstein ND, Fernandez DE, Santoro SW, Needleman LA. 44.  et al. 2015. Quantitative and functional interrogation of parent-of-origin allelic expression biases in the brain. eLife 4:e07860 [Google Scholar]
  45. Pernis B, Chiappino G, Kelus AS, Gell PG. 45.  1965. Cellular localization of immunoglobulins with different allotypic specificities in rabbit lymphoid tissues. J. Exp. Med. 122:5853–76 [Google Scholar]
  46. Reik W, Walter J. 46.  2001. Genomic imprinting: parental influence on the genome. Nat. Rev. Genet. 2:121–32 [Google Scholar]
  47. Rhoades KL, Singh N, Simon I, Glidden B, Cedar H, Chess A. 47.  2000. Allele-specific expression patterns of interleukin-2 and Pax-5 revealed by a sensitive single-cell RT-PCR analysis. Curr. Biol. 10:13789–92 [Google Scholar]
  48. Riviere I, Sunshine MJ, Littman DR. 48.  1998. Regulation of IL-4 expression by activation of individual alleles. Immunity 9:2217–28 [Google Scholar]
  49. Rodriguez I, Feinstein P, Mombaerts P. 49.  1999. Variable patterns of axonal projections of sensory neurons in the mouse vomeronasal system. Cell 97:2199–208 [Google Scholar]
  50. Savova V, Chun S, Sohail M, McCole RB, Witwicki R. 50.  et al. 2016. Genes with monoallelic expression contribute disproportionately to genetic diversity in humans. Nat. Genet. 48:3231–37 [Google Scholar]
  51. Savova V, Patsenker J, Vigneau S, Gimelbrant AA. 51.  2016. dbMAE: the database of autosomal monoallelic expression. Nucleic Acids Res. 44:D1D753–56 [Google Scholar]
  52. Singh N, Ebrahimi FA, Gimelbrant AA, Ensminger AW, Tackett MR. 52.  et al. 2003. Coordination of the random asynchronous replication of autosomal loci. Nat. Genet. 33:3339–41 [Google Scholar]
  53. Spencer HG, Clark AG. 53.  2014. Non-conflict theories for the evolution of genomic imprinting. Heredity 113:2112–18 [Google Scholar]
  54. Stoffregen EP, Donley N, Stauffer D, Smith L, Thayer MJ. 54.  2011. An autosomal locus that controls chromosome-wide replication timing and mono-allelic expression. Hum. Mol. Genet. 20:122366–78 [Google Scholar]
  55. Surani MA, Barton SC, Norris ML. 55.  1984. Development of reconstituted mouse eggs suggests imprinting of the genome during gametogenesis. Nature 308:5959548–50 [Google Scholar]
  56. Varrault A, Gueydan C, Delalbre A, Bellmann A, Houssami S. 56.  et al. 2006. Zac1 regulates an imprinted gene network critically involved in the control of embryonic growth. Dev. Cell 11:5711–22 [Google Scholar]
  57. Wang X, Sun Q, McGrath SD, Mardis ER, Soloway PD, Clark AG. 57.  2008. Transcriptome-wide identification of novel imprinted genes in neonatal mouse brain. PLOS ONE 3:12e3839 [Google Scholar]
  58. Zwemer LM, Zak A, Thompson BR, Kirby A, Daly MJ. 58.  et al. 2012. Autosomal monoallelic expression in the mouse. Genome Biol. 13:2R10 [Google Scholar]

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error