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A closer look at long-range chromosomal interactions

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Abstract

Higher-order chromosome organization is emerging as a major determinant of gene regulation. Although the structure of chromatin at the level of individual nucleosomes has been studied in considerable detail, less is known about higher levels of organization. Two new methods have been developed that can be used to obtain detailed information about the higher-order folding of chromatin. Using these methods, long-range looping interactions have been shown to occur upon activation of the murine β-globin locus, explaining the long-standing question of how gene regulatory elements can act at large genomic distances from their target genes.

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Analysis of chromosome structure by measuring chromosomal interactions

Chromosome structure has been studied extensively by light microscopy, which has provided insights into large-scale organizational features encompassing at least hundreds of kb. X-ray crystallography, however, has been used to determine the high-resolution structure of a single nucleosome [8]. Information about the organization of chromatin at intermediate scales has been difficult to obtain mainly owing to the lack of assays. Now, two new molecular methods make analysis of this level of

Long-range interactions at the β-globin locus

The β-globin locus has been studied in much detail, and an impressive amount of data has been generated regarding the control and activity of the genes in this locus. 3C and RNA TRAP have now been used to analyze the conformation of this locus. The results suggest that the formation of specific chromosome structural features is involved in gene activation.

The murine locus contains four globin-like genes that are differentially expressed during development 9, 10, 11 (Fig. 2a). This locus also

A closer look at chromosomes

The results published by Carter et al. and Tolhuis et al. show that sophisticated structures are involved in controlling gene expression. Similar analyses of other regions will probably unveil chromosome structural features involved in other processes such as DNA replication and repair.

A particularly exciting aspect of RNA TRAP and 3C is that these methods can also be applied to the analysis of chromosome-wide processes such as X-chromosome inactivation and chromosome condensation. Several

Acknowledgements

I thank N. Gheldof, J. Perry and A.J.M Walhout for critical reading of the article and an anonymous referee for valuable comments.

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