Euchromatin

Euchromatin, which can be distinguished from heterochromatin contains the majority of transcriptionally active DNA. Euchromatin, initially identified cytologically during interphase, appears less condensed and stains less intensely with dyes than heterochromatin. Features of euchromatin may be usefully summarized by comparing the active X-chromosome with the inactive X-chromosome.

 The euchromatin of the active X-chromosome contains hyperacetylated histones, which indicate potential for transcriptional activity. The active X-chromosome also contains reduced levels of methylated DNA and replicates early in S-phase. Euchromatin is also likely to be globally sensitive to digestion with nucleases such as DNase I.

 Existence in either the euchromatic or heterochromatic states is not irreversible. This is best demonstrated by experiments in which cells containing nuclei that are predominantly heterochromatic are either transplanted into eggs or fused with other cells that are predominantly euchromatic, to generate a heterokaryon. Experimental results with heterokaryons in which two different somatic cells are fused, so that two different nuclei share a common cytoplasm, and nuclear transplantation experiments using Xenopus eggs have been interpreted as providing evidence for continuous regulation of a plastic differentiated state. Implicit in this model is the idea that all genes are continually regulated by trans-acting factors that can either activate or repress genes (1). For certain genes this is clearly true. It has also been shown, however, that considerable remodeling of chromosomal structure occurs in Xenopus egg and oocyte cytoplasm, during which heterochromatin is converted to euchromatin (2). A similar, albeit less impressive, remodeling of chromosomes occurs in heterokaryons. For example, the nuclei of chicken erythrocytes consist predominantly of heterochromatin containing the specialized linker histone H5. In heterokaryons formed by the fusion of chicken erythrocytes with proliferating mammalian cells, the chicken erythrocyte nuclei once again become transcriptionally active, leading to the appearance of euchromatin (3). This process is accompanied by decondensation of chromatin, enlargement of the nucleus, and the appearance of nucleoli. Transcription and replication of these nuclei are also activated.

 Enlargement of the chicken erythrocyte nucleus is caused by a massive, but selective, uptake of mammalian nuclear proteins, including RNA polymerases. The specialized linker histone H5 is partially lost from the chicken erythrocyte nucleus and partially taken up by the mammalian nucleus in the heterokaryon. Histones H2A and H2B also exchange under these circumstances, but not histones H3 and H4. These results might reflect the relative affinity of the histones for DNA and their organization in the nucleosome. This reorganization is independent of DNA replication. Therefore, it is clear that chromosomal structure is quite dynamic, and some histones (H1, H2A, H2B) continually exchange with a free pool of proteins in the cytoplasm.

 Several experiments suggest that at physiological ionic strength the linker histone H1 rapidly exchanges into and out of the chromatin fiber (5, 6). Histone H1 is a specific repressor for several eukaryotic genes. Presumably this dynamic property of the chromatin fiber and the nucleosome would eventually allow many trans-acting factors to gain access to their cognate DNA sequences. An important and unresolved question is whether this access is unlimited or whether access is restricted by chromosomal organization. It has not yet been quantitatively determined whether the level of transcriptional activity following de novo activation of a gene in a heterokaryon is identical to the transcription of the same gene in a differentiated cell. Of course, in Xenopus egg cytoplasm, such equivalent activation must occur for correct development to proceed through to the tadpole stage. Nuclear reprogramming, however, is more rapid here and is likely to be facilitated by DNA replication (4), although massive nucleus-wide remodeling can occur without concomitant DNA synthesis (7, 8).

References

1. H.M. Blau and D. Baltimore, J. Cell Biol. 112, 781–783 (1991). 

2. J.B. Gurdon, J. Embryol. Exp. Morph. 36, 523–540 (1976). 

3. N.R. Ringertz, U. Nyman, and M. Bergman, Chomosoma 91, 391–396 1985).

4.  S. Dimitrov and A.P. Wolffe, EMBO J. 15, 5897–5906 (1996). 

5. M.A. Lever, J.P. Th''ng,X. Sun, and M.J. Hendzel, Nature 408, 873–876 (2000). 

6. A.P. Wolffe and J.C. Hansen, Cell 104, 631–634 (2001). 

7. N. Kikyo et al., Science 289, 2360–2362 (2000). 

8. N. Kikyo and A.P. Wolffe, J. Cell Sci. 113, 11–20 (2000).