To differentiate different types of chromatin, cells can be stained with DNA-binding chemicals and analyzed by microscopy. Much of the chromatin in interphase cells (about 90% in the case of human cells) shows diffuse staining that can be seen to be dispersed through the nucleus. Chromatin like this, which stains poorly because it is in a comparatively extended state, is called euchromatin (Figure 1A). It is distinguished by relatively weak binding of histone H1 molecules and by extensive acetylation of core nucleosomal histones.
Fig1. Euchromatin, heterochromatin, and higher-level packing of DNA. (A) Transmission electron microscopy of a typical cell nucleus clearly distinguishes the comparatively diffuse euchromatin (EC) from the electron-dense heterochromatin (HC). The euchromatin is dispersed within the interior of the nucleus. The heterochromatin is partly distributed at some interior locations, and includes nucleolus (NU)-associated heterochromatin, but just inside the nuclear envelope is a thin, electron-dense region containing the nuclear lamina and more heterochromatin. Magnification, ×26,000. (B) Alternating regions of open euchromatin and condensed euchromatin are typically found on chromosomes of somatic interphase cells. The open euchromatin can be accessed by RNA polymerase and the transcription machinery, but in the condensed chromatin multiple nucleosomes are tightly packed together and the lengths of linker DNA are significantly reduced. (C) Long regions of very highly-compacted DNA are typical of heterochromatin. (A, from Mescher AL [2018] Junqueira’s Basic Histology: Text and Atlas, 15th edn. Republished with permission of McGraw-Hill Education; permission conveyed through Copyright Clearance Center, Inc.)
In unspecialized cells of the very early embryo, a large proportion of the euchromatin has the “open chromatin” structure shown in Figure 1A, the first level of DNA pack aging, and the only one that will allow transcriptional activity in the cells of eukaryotes. But as cells differentiate and become specialized, the euchromatin is not so uniform: in many regions across chromosomes the euchromatin is significantly condensed, with reduced lengths of linker DNA.
The tight packing of many neighboring nucleosomes in condensed euchromatin means that RNA polymerases and transcription factors may not gain access to potential binding sites on the DNA (Figure 1B). It is the pattern of the open and condensed euchromatin regions across chromosomes that primarily determines which genes are expressed and which are switched off, thereby defining the identity of a cell, whether it be a lymphocyte, hepatocyte, or cardiomyocyte, and so on.
A minority of the chromatin, known as heterochromatin, is revealed as dark- staining regions in microscopy studies (see Figure 1A). It remains highly condensed (Figure 1C) throughout interphase, and is associated with tight binding of histone H1.
The two types of heterochromatin
Most of the heterochromatin in cells is described as constitutive heterochromatin because it is permanently, irreversibly condensed. The associated DNA is gene-poor and consists very largely of highly-repetitive DNA sequences, such as those found in and around the centromeres, telomeres, and over much of the Y chromosome in mammals. Constitutive heterochromatin is consistently genetically inactive in somatic cells, and if through some chromosome rearrangement an actively expressed gene is transposed from a euchromatic region to a heterochromatic region, it is silenced.
Unlike constitutive heterochromatin, facultative heterochromatin has a condensed structure that can be reversed (decondensed) and can be rich in genes. In each somatic cell of female mammals, for example, one of the two X chromosomes is highly condensed as a result of a process known as X-inactivation, and becomes a hetero chromatic chromosome that migrates to the nuclear periphery. But in oogenesis, this chromosome is decondensed and reactivated. (Presumably, having both X chromosomes active is required to permit correct pairing and recombination in meiosis.) Also, both the X and the Y chromosomes become reversibly condensed for about 15 days during meiosis in spermatogenesis, forming the XY body that is segregated into a special nuclear compartment.
