Some reader protein complexes contain a histone-modifying enzyme, such as a histone lysine methylase, that “writes” the same mark that the reader recognizes. A reader–writer–remodeling complex of this type can spread a specific form of chromatin along a chromosome. In particular, large regions of condensed heterochromatin are thought to be formed in this way. Heterochromatin is commonly found around centromeres and near telomeres, but it is also present at many other positions in chromosomes. The tight packaging of DNA into heterochromatin usually silences the genes within it.
The phenomenon of position effect variegation provides strong evidence for the inheritance of condensed states of chromatin from one cell generation to the next. A similar mechanism appears to be responsible for maintaining the specialized chromatin at centromeres. More generally, the ability to propagate specific chromatin structures across cell generations makes possible an epigenetic cell memory process that plays a role in maintaining the set of different cell states required by complex multicellular organisms.
Having discussed the DNA and protein molecules from which the chromatin fiber is made, we now turn to the organization of the chromosome on a more global scale and the way in which its various domains are arranged in space. As a 30-nm fiber, a typical human chromosome would still be 0.1 cm in length and able to span the nucleus more than 100 times. Clearly, there must be a still higher level of folding, even in interphase chromosomes. Although the molecular details are still largely a mystery, this higher-order packaging almost certainly involves the folding of the chromatin into a series of loops and coils. This chromatin packing is fluid, frequently changing in response to the needs of the cell.
We begin this section by describing some unusual interphase chromosomes that can be easily visualized. Exceptional though they are, these special cases reveal features that are thought to be representative of all interphase chromosomes. Moreover, they provide ways to investigate some fundamental aspects of chromatin structure that we have touched on in the previous section. Next, we describe how a typical interphase chromosome is arranged in the mammalian cell nucleus. Finally, we shall discuss the additional tenfold compaction that chromosomes undergo in the passage from interphase to mitosis.
Chromosomes Are Folded into large loops of Chromatin
Insight into the structure of the chromosomes in interphase cells has come from studies of the stiff and enormously extended chromosomes in growing amphibian oocytes (immature eggs). These very unusual lampbrush chromosomes (the largest chromosomes known), paired in preparation for meiosis, are clearly visible even in the light microscope, where they are seen to be organized into a series of large chromatin loops emanating from a linear chromosomal axis (Figure 4–46 and Figure 4–47).
In these chromosomes, a given loop always contains the same DNA sequence that remains extended in the same manner as the oocyte grows. These chromosomes are producing large amounts of RNA for the oocyte, and most of the genes
Figure 4–46 A model for the chromatin domains in a lampbrush chromosome.
Shown is a small portion of one pair of sister chromatids. Here, two identical DNA double helices are aligned side by side, packaged into different types of chromatin. The set of lampbrush chromosomes in many amphibians contains a total of about 10,000 loops resembling those shown here. The rest of the DNA in each chromosome (the great majority) remains highly condensed. Four copies of each loop are present in the cell, since each lampbrush chromosome consists of two aligned sets of paired chromatids. This four-stranded structure is characteristic of this stage of development of the oocyte, which has arrested at the diplotene stage of meiosis; see Figure 17–56.
present in the DNA loops are being actively expressed. The majority of the DNA, however, is not in loops but remains highly condensed on the chromosome axis, where genes are generally not expressed.