Heterochromatin facultative

The mammalian inactive X-chromosomes in females is associated with H3 methylated at Lys-9 but does not have H3 methylated at Lys-4 [165,166]. Deletion of murine Suv39h genes does not affect H3 Lys-9 methylation at the inactive X-chromosome. Thus, different histone methyltransferases are involved in the methylation of H3 Lys-9 in constitutive and facultative heterochromatin [166]. Further, HPl is not associated with the inactive X-chromosome. Methylation of H3 Lys-9 is an early event in X inactivation in mammals [167,168]. The H3 Lys-9 methylation occurs approximately at the same time as H3 Lys-9 hypoacetylation and Lys-4 hypomethylation, and happens before transcriptional inactivation of the X-linked genes. Upstream of the Xist gene, which codes for a strictly nuclear RNA involved in X inactivation, is a constitutive hotspot of H3 methylated at Lys-9. This early event of H3 Lys-9 methylation occurs simultaneously with or immediately following the association of Xist RNA with the X-chromosome. It has been proposed that the hotspot upstream of the Xist gene serves as a nucleation site for the spreading of Xist RNA and methylated Lys-9 H3 [167]. 

The association between a histone tail modification and a particular functional state of chromatin, came with the demonstration that transcriptionally active chromatin fractions were enriched in acetylated histones, firstly by biochemical co-fractionationation ([8,9] and references therein) and then by Chromatin ImmunoPrecipitation, ChIP [10]. Subsequently, regions of transcriptionally silent constitutive and facultative heterochromatin, were shown, by immunofluorescence microscopy, to be under-acetylated [11,12]. This supported the idea that acetylation of the histone tails, with the associated loss of positive charge and reduction in DNA-binding constant, somehow caused chromatin to become more open (or less condensed ) and thereby more conducive to transcription. While this is likely to be an important contributory factor, it has now become clear that the... 

Vaquero, A., Scher, M., Lee, D., Erdjument-Bromage, H., Tempst, P. and Reinberg, D. (2004) Human SirTl interacts with histone HI and promotes formation of facultative heterochromatin. Molecular Cell, 16, 93—105. 

Facultative heterochromatin, such as that found in the second of the X chromosomes of female mammals (XX), does not appear to be present in birds. In mammals, a dosage condensation mechanism operates, which prevents the expression of one of the X chromosomes in the female otherwise females would express two copies of any sex-linked genes. In a normal female mammal (XX constitution), each somatic cell has a single Barr body composed of facultative heterochromatin. The Barr body is a partially or completely condensed X chromosome that is transcriptionally inactive. There is no evidence for an analogous dosage compensation mechanism in birds. No Barr body has yet been identified in a normal male (ZZ) bird, and evidence from a study of the... 

The presence of PARP-2 in r ions of the genome containing repetitive DNA sequences like centromeres, telomeres and rONA and in association with X-chtomosome surest a role of PARP-2 in the maintenance of both constitutive and facultative heterochromatin integrity, which may become a target for pharmacological intervention. 

Peters AH, Mermoud JE, Carroll DO et al. Histone H3 lysine 9 methylation is an epigenetic imprint of facultative heterochromatin. Nature Genet 2002 30 77-80. 

T. Haaf and M. Schmid, Experimental condensation inhibition in constitutive and facultative heterochromatin of mammalian chromosomes, Cytogenet. Cell Genet., 2000, 91, 113-123. 

In birds, the female possesses the heteromorphic pair of chromosomes, having the Z and W sex chromosomes, whereas the male has a pair of Z chromosomes. The W chromosome is much smaller than the Z chromosome, being the size of a microchromosome. In most species examined, the W chromosome also has a high proportion of heterochromatin, usually GC-rich (Fritschi Stranzinger, 1985 Auer et al., 1987 Mayr et al., 1989 1990). Chandra (1994) suggests that the W sex chromosome shows the characteristics of an inactive chromosome in somatic cells and could be regarded as facultative helerochromatin. 

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