In those species (including humans) in which sex is determined by the presence of the Y or W chromosome rather than the diploidy of the X or Z, a Barr body is the inactive X chromosome in a female cell, or the inactive Z in a male (Lyon, 2003), rendered inactive in a process called Lyonization. The Lyon hypothesis states that in cells with multiple X chromosomes, all but one is inactivated during mammalian embryogenesis (Lyon, 1961). This happens early in embryonic development at random in mammals, (Brown, 1997) except in marsupials and in some extra-embryonic tissues of some placental mammals, in which the father's X chromosome is always deactivated (Lee, 2003). Barr bodies are named after their discoverer, Murray Barr (Barr & Bertram, 1949). Figure 1: A representation of a condensed eukaryotic chromosome, as seen during cell division. ... The Haplodiploid sex-determination system is a system that some Hymenopterans (bees, ants, and wasps), and coleopterans (bark beetles) use to determine the sex of their offspring, and preserve eusociality. ... The Lyon hypothesis states that in cells with multiple X chromosomes, all but one is inactivated during mammalian embryogenesis. ... ‹ The template below (Expand) is being considered for deletion. ... Embryogenesis is the process by which the embryo is formed and develops. ... For other uses, see Embryo (disambiguation). ... Subclasses & Infraclasses Subclass †Allotheria* Subclass Prototheria Subclass Theria Infraclass †Trituberculata Infraclass Metatheria Infraclass Eutheria Mammals (class Mammalia) are warm-blooded, vertebrate animals characterized by the presence of sweat glands, including those that produce milk, and by the presence of: hair, three middle ear bones used in hearing, and a neocortex... This article is about mammals. ... Murray Llewellyn Barr (June 20, 1908 – May 4, 1995) was a Canadian physician and medical researcher, who discovered, in 1948, an important cell structure, the Barr body. Born in Belmont, Ontario, he was educated at the University of Western Ontario, where he received his B.A. in 1930, M.D...

The inactivation state of chromosomes is passed on to daughter cells during mitosis (Hall et al., 2003). Since random chromosomes are selected for inactivation early in embryonic development, this results in different regions of the adult body having different chromosomes inactivated. This can be significant if different alleles of a gene are present on the different chromosomes; in some regions of the body one allele will be active, and in other regions the other will. This is what results in the coloration pattern of female calico cats; pigmentation genes on the X chromosome are activated in different patches of skin based on which chromosome is condensed in those regions (Alberts et al., 2002). Mitosis is the way that in which a cell duplicates its chromosomes to generate two identical nuclei. ... For the hard rock band, see Allele (band). ... Tortoiseshell is a coloring found in cats caused by a combination of specific genetic traits. ...

The Barr body chromosome is generally considered to be inert, but in fact a small number of genes remain active and expressed in some species. These genes are generally those which are present on the other sex chromosome (Y or W) (Lyon, 2003).

Mechanism

Mammalian X-chromosome inactivation is initiated from the X inactivation centre or Xic, usually found near the centromere (Rougeulle et al., 2003). The centre contains twelve genes, seven of which code for proteins, five for untranslated RNAs, of which only two are known to play an active role in the X inactivation process, Xist and Tsix (Rougeulle et al., 2003). The centre also appears to be important in chromosome counting: ensuring that random inactivation only takes place when two X-chromosomes are present. The provision of an extra artificial Xic in early embryogenesis can induce inactivation of the single X found in male cells (Rougeulle et al., 2003). ‹ The template below (Expand) is being considered for deletion. ... The centromere is a region of chromosomes with a special sequence and structure. ... For other uses, see Gene (disambiguation). ... A representation of the 3D structure of myoglobin, showing coloured alpha helices. ... Ribonucleic acid or RNA is a nucleic acid polymer consisting of nucleotide monomers that plays several important roles in the processes that translate genetic information from deoxyribonucleic acid (DNA) into protein products; RNA acts as a messenger between DNA and the protein synthesis complexes known as ribosomes, forms vital portions... Xist is an RNA gene on the X chromosome of the placental mammals that acts as major effector of the X inactivation process. ... Embryogenesis is the process by which the embryo is formed and develops. ...

The roles of Xist and Tsix appear to be antagonistic. The loss of Tsix expression on the future inactive X chromosome results in an increase in levels of Xist around the Xic. Meanwhile, on the future active X Tsix levels are maintained; thus the levels of Xist remain low. (Lee et al, 1999) This shift allows Xist to begin coating the future inactive chromosome, spreading out from the Xic (Lyon, 2003). In non-random inactivation this choice appears to be fixed and current evidence suggests that the maternally inherited gene may be imprinted (Brown, 1997). For other uses, see Gene (disambiguation). ... Genomic imprinting is a genetic phenomenon involved in the control of a small proportion of genes in the genome, where the allele that is expressed is determined solely on which parent contributes it. ...

It is thought that this constitutes the mechanism of choice, and allows downstream processes to establish the compact state of the Barr body. These changes include histone modifications, such as histone H3 methylation (Heard et al., 2001) and histone H2A ubiquitination, (de Napoles et al., 2004) as well as direct modification of the DNA itself, via the methylation of CpG sites (Chadwick et al., 2003). These changes help inactivate gene expression on the inactive X-chromosome and to bring about its compaction to form the Barr body. Schematic representation of the assembly of the core histones into the nucleosome. ... Methylation is a term used in the chemical sciences to denote the attachment or substitution of a methyl group on various substrates. ... // Background Ubiquitylation, also termed ubiquitination, refers to the process particular to eukaryotes whereby a protein is post-translationally modified by covalent attachment of a small protein. ... The structure of part of a DNA double helix Deoxyribonucleic acid, or DNA, is a nucleic acid molecule that contains the genetic instructions used in the development and functioning of all known living organisms. ... CpG sites are regions of the DNA where a cytosine nucleotide is situated next to a guanine nucleotide. ... For other uses, see Gene (disambiguation). ...

See also

• X-inactivation
• Sex-determination system
• Demethylation
• Acetylation

In those species in which sex is determined by the presence of the Y or W chromosome rather than the diploidy of the X or Z, a Barr body is the inactive X chromosome in a female cell, or the inactive Z in a male. ... A sex-determination system is a biological system that determines the development of sexual characteristics in an organism. ... Demethylation is the chemical process resulting in the removal a methyl group (CH3) from a molecule. ... Acetylation describes a reaction, usually with acetic acid, that introduces an acetyl functional group into an organic compound. ...

References

Links to full text articles are provided where access is free, in other cases only the abstract has been linked.

• Alberts,B., Johnson,A., Lewis,J., Raff,M., Roberts,K., Walter,P., (2002), Molecular Biology of the Cell, Fourth Edition, (428-429) Garland Science, 0-8153-4072-9 (Web Edition, Free access)

• Barr, M. L., Bertram, E. G., (1949), A Morphological Distinction between Neurones of the Male and Female, and the Behaviour of the Nucleolar Satellite during Accelerated Nucleoprotein Synthesis. Nature. 163 (4148): 676-7.

• Brown,C.J., Robinson,W.P., (1997), XIST Expression and X-Chromosome Inactivation in Human Preimplantation Embryos. Am. J. Hum. Genet. 61, 5-8 (Full Text PDF)

• Chadwick,B.P., Willard,H.F., (2003), Barring gene expression after XIST: maintaining faculative heterochromatin on the inactive X. j.semcdb 14, 359-367 (Abstract)

• de Napoles,M., Mermoud,J.E., Wakao,R., Tang,Y.A., Endoh,M., Appanah,R., Nesterova,T.B., Silva,J., Otte,A.P., Vidal,M., Koseki,H., Brockdorff,N., (2004), Polycomb Group Proteins Ring1A/B Link Ubiquitylation of Histone H2A to Heritable Gene Silencing and X Inactivation. Dev. Cell 7, 663-676 (Abstract)

• Hall,L.L., Lawrence,J.B., (2003), The Cell Biology of a Novel Chromosomal RNA: Chromosome Painting By XIST/Xist RNA Initiates a remodeling cascade. j.semcdb 14, 369-378 (Abstract)

• Heard, E., Rougeulle, C., Arnaud, D., Avner, P., Allis, C. D. (2001), Methylation of Histone H3 at Lys-9 Is an Early Mark on the X Chromosome during X Inactivation. Cell 107, 727-738. (Full Text)

• Lee, J. T., Davidow, L. S., Warshawsky, D., (1999), Tisx, a gene antisense to Xist at the X-inactivation centre. Nat. Genet. 21, 400-404. Full Text

• Lee, J. T., (2003), X-chromosome inactivation: a multi-disciplinary approach. j.semcdb 14, 311-312. (doi:10.1016/j.semcdb.2003.09.025 Abstract)

• Lyon, M. F. (1961), Gene Action in the X-chromosome of the Mouse (Mus musculus L.) Nature. 190 (4773): 372-3. PMID 13764598 (Abstract)

• Lyon, M. F., (2003), The Lyon and the LINE hypothesis. j.semcdb 14, 313-318. (Abstract)

• Rougeulle, C., Avner, P. (2003), Controlling X-inactivationin mammals: what does the centre hold?. j.semcdb 14, 331-340. (Abstract)