The term heterochromatin is often used incorrectly to describe transcriptionally silent chromatin. Repressed genes do have similar protein factors associated with them as heterochromatin but in many cases only a short region of the chromatin fibre is 'closed'. Therefore, in terms of the cell nucleus these regions do not constitute domains of heterochromatin particularly when it is possible to re-open these sequences and express the genes in the loci. In contrast true heterochromatin covers a large region of chromatin which is able to form a repressive domain within the nucleus. The silencing of other genes can be facilitated by translocating them into these silenced domains (often in the centre of chromosome territories) whilst transcriptionally active genes and genes which can be reactivated are found outwith these regions of silencing (often on the surface of chromosome territories).
We are currently working on a component of the HuCHRAC chromatin remodelling complex (ACF) which has been localised to heterochromatin (Poot et al., 2000
). One idea is that this complex facilitates the regular positioning of nucleosomes within heterochromatin thereby allowing the stable formation of a chromatin structure. Alternatively, heterochromatin might act as a sink for protein complexes which are required for repressing gene transcription such as histone deacetylases and nucleosome remodelling machines.
In our lab, one of our topics of interest is to explore heterochromatin to determine its conformation and the factors responsible for generating its structure and to understand how these might be involved in determining centromere identity (Choo, 2001; Sullivan et al., 2001)
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Thomas Jenuwein Lab
REFERENCES
Bernard,P., Maure,J.F., Partridge,J.F., Genier,S., Javerzat,J.P., and Allshire,R.C. (2001) Requirement of heterochromatin for cohesion at centromeres. Science 294, 2539-2542
Bickmore,W.A. and Craig,J.M. (1997). Chromosome Bands: Patterns in the Genome. (Heidelberg: Springer).
Choo,K.H. (2001) Domain organization at the centromere and neocentromere. Dev. Cell 1, 165-177
Choo,K.H.A. (1997). The Centromere. (Oxford: Oxford University Press).
Eissenberg,J.C. and Elgin,S.C. (2000) The HP1 protein family: getting a grip on chromatin. Curr. Opin. Genet. Dev. 10, 204-210
Gilbert,N. and Allan,J. (2001) Distinctive higher-order chromatin structure at mammalian centromeres. Proc. Natl. Acad. Sci. U. S. A 98, 11949-11954
Nielsen,A.L., Oulad-Abdelghani,M., Ortiz,J.A., Remboutsika,E., Chambon,P., and Losson,R. (2001) Heterochromatin formation in mammalian cells: interaction between histones and HP1 proteins. Mol. Cell 7, 729-739
Peters,A.H., O'Carroll,D., Scherthan,H., Mechtler,K., Sauer,S., Schofer,C., Weipoltshammer,K., Pagani,M., Lachner,M., Kohlmaier,A., Opravil,S., Doyle,M., Sibilia,M., and Jenuwein,T. (2001) Loss of the Suv39h histone methyltransferases impairs mammalian heterochromatin and genome stability. Cell 107, 323-337
Poot,R.A., Dellaire,G., Hulsmann,B.B., Grimaldi,M.A., Corona,D.F., Becker,P.B., Bickmore,W.A., and Varga-Weisz,P.D. (2000) HuCHRAC, a human ISWI chromatin remodelling complex contains hACF1 and two novel histone-fold proteins. EMBO J. 19, 3377-3387
Sullivan,B.A., Blower,M.D., and Karpen,G.H. (2001) Determining centromere identity: cyclical stories and forking paths. Nat. Rev. Genet. 2, 584-596.
Van Holde,K.E. (1988). Chromatin. (New York: Springer Verlag).
Wolffe,A.P. (1995). Chromatin structure and function. (London: Academic Press).
Zhang,Y. and Reinberg,D. (2001) Transcription regulation by histone methylation: interplay between different covalent modifications of the core histone tails. Genes Dev. 15, 2343-2360.