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

TRANSCRIPTION REGULATORS SWITCH GENES ON AND OFF
387
NUCLEOSOME SLIDING ALLOWS
ACCESS OF TRANSCRIPTION
MACHINERY TO DNA
remodeled nucleosomes
transcription regulator
chromatin remodeling
complex
histone chaperone
histone chaperone
TATA
nucleosome removal
TRANSCRIPTION MACHINERY
ASSEMBLES ON
NUCLEOSOME-FREE DNA
TATA
TATA
HISTONE VARIANTS ALLOW
GREATER ACCESS TO
NUCLEOSOMAL DNA
histone-modifying
enzyme
histone replacement
specific pattern of
histone modification
SPECIFIC PATTERNS OF HISTONE
MODIFICATION DESTABILIZE
COMPACT FORMS OF CHROMATIN
AND ATTRACT COMPONENTS
OF TRANSCRIPTION MACHINERY
promoters (Figure 7–19). These local alterations in chromatin structure provide
greater access to DNA, thereby facilitating the assembly of the general transcription
factors at the promoter. In addition, some histone modifications specifically
attract these proteins to the promoter. These mechanisms often work together
during transcription initiation (Figure 7–20). Finally, as discussed earlier in this
chapter, the local chromatin changes directed by one transcriptional regulator
can allow the binding of additional regulators. By repeated use of this principle,
large assemblies of proteins can form on control regions of genes to regulate their
transcription.
The alterations of chromatin structure that occur during transcription initiation
can persist for different lengths of time. In some cases, as soon as the transcription
regulator dissociates from DNA, the chromatin modifications are rapidly
reversed, restoring the gene to its pre-activated state. This rapid reversal is especially
important for genes that the cell must quickly switch on and off in response
to external signals. In other cases, the altered chromatin structure persists, even
after the transcription regulator that directed its establishment
MBoC6 m7.46/7.20has dissociated
from DNA. In principle, this memory can extend into the next cell generation
because, as discussed in Chapter 4, chromatin structure can be self-renewing
(see Figure 4–44). The fact that different histone modifications persist for different
times provides the cell with a mechanism that makes possible both longer- and
shorter-term memory of gene expression patterns.
A special type of chromatin modification occurs as RNA polymerase II transcribes
through a gene. The histones just ahead of the polymerase can be acetylated
by enzymes carried by the polymerase, removed by histone chaperones,
and deposited behind the moving polymerase. These histones are then rapidly
deacetylated and methylated, also by complexes that are carried by the polymerase,
leaving behind nucleosomes that are especially resistant to transcription.
This remarkable process seems to prevent spurious transcription reinitiation
Figure 7–19 Eukaryotic transcription
activator proteins direct local alterations
in chromatin structure. Nucleosome
remodeling, nucleosome removal, histone
replacement, and certain types of histone
modifications favor transcription initiation
(see Figure 4–39). These alterations
increase the accessibility of DNA and
facilitate the binding of RNA polymerase
and the general transcription factors.