Cell division, heterochromatin

In the nuclei of eukaryotes (see p. 196), DNA is closely associated with proteins and RNA. These nucleoprotein complexes, with a DNA proportion of approximately one-third, are known as chromatin. It is only during cell division (see p. 394) that chromatin condenses into chromosomes that are visible under light microscopy. During interphase, most of the chromatin is loose, and in these conditions a morphological distinction can be made between tightly packed heterochromatin and the less dense euchromatin. Euchro-matin is the site of active transcription. 

An essential instrument for the suppression of transcription activity in heterochromatin, as well as for the differential regulation in euchromatin, is the methylation of DNA on the C5 atom of cytidine in the CpG sequence (Fig. 1.43). CpG sequences occur imevenly distributed in the genome. They may be concentrated in CpG islands. Higher eucaryotes possess a characteristic distribution pattern of 5-methyl cytidine (m C), which remains intact upon cell division. Mechanisms must therefore exist to ensure that the methylation pattern is precisely retained in the daughter cells following cell division. A methyl transferase that carries out hemi-methylation in the CpG sequences (Fig. 1.43) is responsible for the inheritance of the methylation pattern. The methyl group is derived from S-adenosyl methionine. The preferential substrates for the hemi-methylation are DNA sequences in which the complementary strand is already methylated. Such a hemi-methylation occurs, for example, shortly after replication of the sequence. 

From these autoradiographic observations several features of chromosome replication are apparent. There is a heritable pattern of chromosome replication in eukaryote cells that is repeated in successive cell division cycles. However, this pattern can vary depending on the developmental stage of the cell. This variation in the chromosome replication pattern appears to be related to the condensation cycle of a chromosome, i.e., heterochromatinization of a chromosome results in the late replication of that chromosome. 

Chromatin the stainable material of the interphase nucleus, consisting of DNA, RNA and several specialized proteins, which is dispersed randomly in the nucleus. The chromosomal DNA is intact in this phase it is merely uncoiled or relaxed . Immediately prior to cell division, C. condenses into dense bodies (chromosomes), which can be intensely stained. Heterochromatin is tightly coiled and densely packed chromosomal material which is not being transcribed. Euchromatin has a looser structure and is the site of transcription. See Nucleosomes. See Chromosome. 

Anaviev and Gvozdev (1974 a) have studied the position effect of the mosaic type in D. melanogaster with the chromosomal mutation Dp (l f)R and the translocation of the euchromatic region 1A3-4-3A1-2 of the X chromosome to the centromere heterochromatin. According to their data, there is a delay of replication of the translocated euchromatin. RNA synthesis here was reduced to 60% of normal. These data show that the position effect is accompanied by alterations at the transcriptional level. The resistance of the eye mosaic peculiarities to inhibitors of cell division and RNA synthesis added at the end of the first larval stage does not contradict the above statements (Baker, 1967 Perez-Davila and Baker, 1967). 

In the telophase, the chromosomes begin to leave the condensed state, a nuclear membrane is reestablished, and the cell membrane dividing the cell is reformed the actual cell division is termed cytokinesis and can be inhibited by cytochalasin-B, yielding binucleate cells (Rao and Smith, 1976). Cytokinesis rapidly follows mitosis. A portion of the chromatin remains condensed and is termed heterochromatin. The inactive X chromosome of females is an example of heterochromatin and is the so-called Barr body (Barr and Bertram, 1949). Heterochromatin is distinguished from unwound or dispersed chromatin, which is the euchromatin. 

The phenotype of differentiated Thl and Th2 cells is stabilized after about 3-5 divisions [14]. Early in the differentiation, 114 and IFNy loci are easily accessible 114 and IFNy genes are localized away from the silenced centromeric chromatin. Conversely, in Thl cells, 52% of 114 alleles are reorganized in apposition to centromeric heterochromatin and in Th2 cells 67% of IFN-y alleles are directed to heterochromatic domains, which... 

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