A Barr body (named after discoverer Murray Barr) or X-chromatin is an inactive

X chromosome The X chromosome is one of the two sex-determining chromosomes (allosomes) in many organisms, including mammals (the other is the Y chromosome), and is found in both males and females. It is a part of the XY sex-determination system and XO sex ...

in a cell with more than one X chromosome, rendered inactive in a process called lyonization, in species with XY sex-determination (including humans). The Lyon hypothesis states that in cells with multiple

s, all but one are inactivated during mammalian

embryogenesis An embryo is an initial stage of development of a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male spe ...

. This happens early in

embryo An embryo is an initial stage of development of a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male spe ...

nic development at random in

mammal Mammals () are a group of vertebrate animals constituting the class Mammalia (), characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fur ...

s,Brown, C.J., Robinson, W.P., (1997), XIST Expression and X-Chromosome Inactivation in Human Preimplantation Embryos ''Am. J. Hum. Genet.'' 61, 5–8
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except in

marsupial Marsupials are any members of the mammalian infraclass Marsupialia. All extant marsupials are endemic to Australasia, Wallacea and the Americas. A distinctive characteristic common to most of these species is that the young are carried in ...

s and in some extra-embryonic tissues of some placental mammals, in which the X chromosome from the sperm is always deactivated. In humans with

euploidy Ploidy () is the number of complete sets of chromosomes in a cell, and hence the number of possible alleles for autosomal and pseudoautosomal genes. Sets of chromosomes refer to the number of maternal and paternal chromosome copies, respectivel ...

, a

genotypical The genotype of an organism is its complete set of genetic material. Genotype can also be used to refer to the alleles or variants an individual carries in a particular gene or genetic location. The number of alleles an individual can have in a ...

female (46, XX

karyotype A karyotype is the general appearance of the complete set of metaphase chromosomes in the cells of a species or in an individual organism, mainly including their sizes, numbers, and shapes. Karyotyping is the process by which a karyotype is disce ...

) has one Barr body per somatic

cell nucleus The cell nucleus (pl. nuclei; from Latin or , meaning ''kernel'' or ''seed'') is a membrane-bound organelle found in eukaryotic cells. Eukaryotic cells usually have a single nucleus, but a few cell types, such as mammalian red blood cells, h ...

, while a genotypical male (46, XY) has none. The Barr body can be seen in the

interphase Interphase is the portion of the cell cycle that is not accompanied by visible changes under the microscope, and includes the G1, S and G2 phases. During interphase, the cell grows (G1), replicates its DNA (S) and prepares for mitosis (G2). A c ...

nucleus as a darkly staining small mass in contact with the nucleus membrane. Barr bodies can be seen in

neutrophils Neutrophils (also known as neutrocytes or heterophils) are the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. They form an essential part of the innate immune system, with their functions varying ...

at the rim of the nucleus. In humans with more than one X chromosome, the number of Barr bodies visible at interphase is always one fewer than the total number of X chromosomes. For example, people with

Klinefelter syndrome Klinefelter syndrome (KS), also known as 47,XXY, is an aneuploid genetic condition where a male has an additional copy of the X chromosome. The primary features are infertility and small, poorly functioning testicles. Usually, symptoms are sub ...

(47, XXY) have a single Barr body, and people with a 47, XXX karyotype have two Barr bodies.

Mechanism

Someone with two X chromosomes (such as most

human Humans (''Homo sapiens'') are the most abundant and widespread species of primate, characterized by bipedalism and exceptional cognitive skills due to a large and complex brain. This has enabled the development of advanced tools, cultu ...

females) has only one Barr body per

somatic cell A somatic cell (from Ancient Greek σῶμα ''sôma'', meaning "body"), or vegetal cell, is any biological cell forming the body of a multicellular organism other than a gamete, germ cell, gametocyte or undifferentiated stem cell. Such cells com ...

, while someone with one X chromosome (such as most human males) has none. Mammalian

X-chromosome inactivation X-inactivation (also called Lyonization, after English geneticist Mary Lyon) is a process by which one of the copies of the X chromosome is inactivated in therian female mammals. The inactive X chromosome is silenced by being packaged into a ...

is initiated from the X inactivation centre or ''Xic'', usually found near the

centromere The centromere links a pair of sister chromatids together during cell division. This constricted region of chromosome connects the sister chromatids, creating a short arm (p) and a long arm (q) on the chromatids. During mitosis, spindle fibers ...

. The center contains twelve

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

s, seven of which code for

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...

s, five for untranslated RNAs, of which only two are known to play an active role in the X inactivation process, '' Xist'' and ''

Tsix Tsix is a non-coding RNA gene that is antisense to the Xist RNA. Tsix binds Xist during X chromosome inactivation. The name Tsix comes from the reverse of Xist, which stands for X-inactive specific transcript. Background Female mammals have ...

''. The centre also appears to be important in chromosome counting: ensuring that random inactivation only takes place when two or more X-chromosomes are present. The provision of an extra artificial ''Xic'' in early

can induce inactivation of the single X found in male cells. 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. This shift allows ''Xist'' to begin coating the future inactive chromosome, spreading out from the ''Xic''. In non-random inactivation this choice appears to be fixed and current evidence suggests that the maternally inherited

may be imprinted. Variations in Xi frequency have been reported with age, pregnancy, the use of oral contraceptives, fluctuations in menstrual cycle and neoplasia. 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 In biology, histones are highly basic proteins abundant in lysine and arginine residues that are found in eukaryotic cell nuclei. They act as spools around which DNA winds to create structural units called nucleosomes. Nucleosomes in turn a ...

modifications, such as histone H3

methylation In the chemical sciences, methylation denotes the addition of a methyl group on a substrate, or the substitution of an atom (or group) by a methyl group. Methylation is a form of alkylation, with a methyl group replacing a hydrogen atom. These ...

(i.e. H3K27me3 by PRC2 which is recruited by Xist) and histone H2A

ubiquitination Ubiquitin is a small (8.6 kDa) regulatory protein found in most tissues of eukaryotic organisms, i.e., it is found ''ubiquitously''. It was discovered in 1975 by Gideon Goldstein and further characterized throughout the late 1970s and 1980s. Fo ...

, as well as direct modification of the DNA itself, via the methylation of

CpG site The CpG sites or CG sites are regions of DNA where a cytosine nucleotide is followed by a guanine nucleotide in the linear sequence of bases along its 5' → 3' direction. CpG sites occur with high frequency in genomic regions called CpG isl ...

s. These changes help inactivate

expression on the inactive X-chromosome and to bring about its compaction to form the Barr body. Reactivation of a Barr body is also possible, and has been seen in breast cancer patients. One study showed that the frequency of Barr bodies in breast carcinoma were significantly lower than in healthy controls, indicating reactivation of these once inactivated X chromosomes.

References

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

Mechanism

See also

References

Further reading