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

200 Chapter 4: DNA, Chromosomes, and Genomes
protein modules
binding to specific
histone modifications
on nucleosome
covalent
modification
on histone tail
(mark)
scaffold
protein
READER PROTEIN
BINDS AND
ATTRACTS OTHER
COMPONENTS
reader
complex
protein complex with
catalytic activities and
additional binding sites
Figure 4–38 Schematic diagram showing
how a particular combination of histone
modifications can be recognized by a
reader complex. A large protein complex
that contains a series of protein modules,
each of which recognizes a specific histone
mark, is schematically illustrated (green).
This “reader complex” will bind tightly only
to a region of chromatin that contains
several of the different histone marks that
it recognizes. Therefore, only a specific
combination of marks will cause the
complex to bind to chromatin and attract
the additional protein complexes (purple)
needed to catalyze a biological function.
attachment to other components in nucleus,
leading to gene expression, gene silencing,
or other biological function
see Figure 7–20). But after a modifying enzyme “writes” its mark on one or a few
neighboring nucleosomes, events that resemble a chain reaction can ensue. In
such a case, the “writer enzyme” works in concert with a “reader protein” located
in the same protein complex. The reader protein contains a module that recognizes
the mark and binds tightly to the newly modified nucleosome (see Figure
(A)
A
M A A A
A
M
M M P MMBoC6 M m4.43/4.36 M M P
R K KS
K RK K RKS
K
2 4 910 14 1718 23 262728 36
(B) modification state “meaning”
trimethyl
M
trimethyl
M
K
9
A
K K
4 9
trimethyl
M
K
27
M
heterochromatin formation,
gene silencing
gene expression
gene silencing
(Polycomb repressive complex)
histone
H3
Figure 4–39 Some specific meanings
of histone modifications. (A) The
modifications on the histone H3 N-terminal
tail are shown, repeated from Figure
4–34. (B) The H3 tail can be marked by
different sets of modifications that act in
combination to convey a specific meaning.
Only a small number of the meanings
are known, including the three examples
shown. Not illustrated is the fact that, as
just implied (see Figure 4–38), reading a
histone mark generally involves the joint
recognition of marks at other sites on the
nucleosome along with the indicated H3
tail recognition. In addition, specific levels
of methylation (mono-, di-, or trimethyl
groups) are generally required. Thus,
for example, the trimethylation of lysine
9 attracts the heterochromatin-specific
protein HP1, which induces a spreading
wave of further lysine 9 trimethylation
followed by further HP1 binding, according
to the general scheme that will be
illustrated shortly (see Figure 4–40). Also
important in this process, however, is a
synergistic trimethylation of the histone H4
N-terminal tail on lysine 20.