Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

194 Chapter 4: DNA, Chromosomes, and Genomes
CHROMATIN STRUCTURE AND FUNCTION
Having described how DNA is packaged into nucleosomes to create a chromatin
fiber, we now turn to the mechanisms that create different chromatin structures
in different regions of a cell’s genome. Mechanisms of this type have a variety of
important functions in cells. Most strikingly, certain types of chromatin structure
can be inherited; that is, the structure can be directly passed down from a cell
to its descendants. Because the cell memory that results is based on an inherited
chromatin structure rather than on a change in DNA sequence, this is a form
of epigenetic inheritance. The prefix epi is Greek for “on”; this is appropriate,
because epigenetics represents a form of inheritance that is superimposed on the
genetic inheritance based on DNA.
In Chapter 7, we shall introduce the many different ways in which the expression
of genes is regulated. There we discuss epigenetic inheritance in detail and
present several different mechanisms that can produce it. Here, we are concerned
with only one, that based on chromatin structure. We begin this section by
reviewing the observations that first demonstrated that chromatin structures can
be inherited. We then describe some of the chemistry that makes this possible—
the covalent modification of histones in nucleosomes. These modifications have
many functions, inasmuch as they serve as recognition sites for protein domains
that link specific protein complexes to different regions of chromatin. Histones
thereby have effects on gene expression, as well as on many other DNA-linked
processes. Through such mechanisms, chromatin structure plays an important
role in the development, growth, and maintenance of all eukaryotic organisms,
including ourselves.
Heterochromatin Is Highly Organized and Restricts Gene
Expression
Light-microscope studies in the 1930s distinguished two types of chromatin in
the interphase nuclei of many higher eukaryotic cells: a highly condensed form,
called heterochromatin, and all the rest, which is less condensed, called euchromatin.
Heterochromatin represents an especially compact form of chromatin
(see Figure 4–9), and we are finally beginning to understand its molecular properties.
It is highly concentrated in certain specialized regions, most notably at the
centromeres and telomeres introduced previously (see Figure 4–19), but it is also
present at many other locations along chromosomes—locations that can vary
according to the physiological state of the cell. In a typical mammalian cell, more
than 10% of the genome is packaged in this way.
The DNA in heterochromatin typically contains few genes, and when euchromatic
regions are converted to a heterochromatic state, their genes are generally
switched off as a result. However, we know now that the term heterochromatin
encompasses several distinct modes of chromatin compaction that have different
implications for gene expression. Thus, heterochromatin should not be thought
of as simply encapsulating “dead” DNA, but rather as a descriptor for compact
chromatin domains that share the common feature of being unusually resistant
to gene expression.
The Heterochromatic State Is Self-Propagating
Through chromosome breakage and rejoining, whether brought about by a natural
genetic accident or by experimental artifice, a piece of chromosome that is
normally euchromatic can be translocated into the neighborhood of heterochromatin.
Remarkably, this often causes silencing—inactivation—of the normally
active genes. This phenomenon is referred to as a position effect. It reflects a
spreading of the heterochromatic state into the originally euchromatic region,
and it has provided important clues to the mechanisms that create and maintain
heterochromatin. First recognized in Drosophila, position effects have now been
observed in many eukaryotes, including yeasts, plants, and humans.