Lewin Benjamin (ed.) Genes IX
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with chromatin assembly factor ASFI. Gen es
Dev. 15,
ll55-1I68.
Histone Acetytation
Occurs
in Two
Circumstances
Reviews
Hirose, Y. and Manley,
J.
L.
(2000).
RNA
poly-
merase II and
the
integration
of nuclear
events. Genes
Dev. 14, l415-1429.
Verreault, A.
(2000).
De novo nucleosome assem-
bly: new
pieces
in an old
puzzle.
Genes
Dev. 14,
r430-14J8.
Resea rch
Akhtar, A. and Becker, P. B.
(2000).
Activation of
transcription
through histone H4
acetylation
by MOF, an acetyltransferase essential for
dosage compensation in Drosophila. Mol. Cell 5,
j67-)75.
Alwine, J. C., I(emp, D. J., and Stark,
G.
R.
(1977).
Method for detection of specific RNAs in
agarose
gels
by transfer to diazobenzyl-
oxymethyl-paper
and hybridization
with
DNA
probes.
Proc Natl- Acad.
Sci USA74,
5)50-5354.
Jackson,
V., Shires, A., Tanphaichitr, N., and
Chalkley,
R.
(1976).
Modifications to histones
immediately after synthesis. J Mol Biol. lO4,
47 r-48).
Ling, X., Harkness,
T. A.,
Schultz,
M.
C.,
Fisher-
Adams, G., and Grunstein, M.
(1996).
Yeast
histone
H3
and
H4
amino termini are
impor-
tant for
nucleosome
assembly in vivo and
in
vilro: redundant and
position-independent
functions in assembly but not in
gene
regula-
tion.
Genes Dev. 10,686-699.
Shibahara,
I(., Verreault, A., and Stillman, B.
(2000).
The
N-terminal domains of
histones
H3 and H4 are not necessary for chromatin
assembly
factor- I
-mediated
nucleosome
assembly
onto replicated DNA in vitro.
Proc
Natl.
Acad. Sci. USA 97
,
77 66-777 L
Turner,
B. M., Birley, A. J., and Lavender, J.
ll992l.
Histone
H4 isoforms
acetylated
at spe-
cific
lysine residues define individual chromo-
somes and chromatin domains
in Drosophila
polytene nuclei.
Cell 69,375-384.
Acetytases Are Associated with
Activators
Resea
rc h
Brownell, J. E. et al.
(1996).
Tetrahymena histone
acetyltransferase
A:
a
homologue
to
yeast
Gcn5p
linking
histone
acetylation to
gene
activation. Cell 84, 843-851.
Chen,
H. etal,.
(1997).
Nuclear
receptor coactiva-
tor
ACTR is a novel histone acetyltransferase
and forms a
multimeric activation complex
with
P/CAF and CP/p300. Cell 90, 569-580.
Grant, P. A. et al.
(1998).
A
subset
of
TAFlys are
integral components
of the
SAGA
complex
required for
nucleosome
acetylation
and tran-
scriptional
stimulation.
Cell
94, 45-53.
I(ingston, R.
E.
and
Narlikar,
G. J.
(1999). ATP-
dependent
remodeling
and acetylation
as
reg-
ulators
of chromatin
fluidity. Genes
Dev. 13,
2))9-2352.
Lee, T. L, Causton,
H. C.,
Holstege,
F. C., Shen,
W C., Hannett,
N., Jennings,
E. G., Winston,
F.,
Green,
M. R.,
and
Young, R.
A.
(2000).
Redundant roles
for the
TFID and
SAGA
complexes
in
global
transcription.
Nature
405,
70t-704.
Deacetytases
Are
Associated
with
ReDressors
Review
Richards,
E. J., Elgin,
S. C.,
and
Richards, S. C.
(2OO2l
. Epigenetic
codes
for
heterochromatin
formation
and silencing:
rounding
up the
usual suspects.
Cell
lO8, 489-500.
Resea rch
Ayer, D. E., Lawrence,
Q.
A., and
Eisenman,
R.
N.
(
I
99 5
)
. Mad-Max
transcriptional
repression
is
mediated
by ternary
complex
formation
with
mammalian
homologs
of
yeast
repressor
Sin3.
Cell 80,767-776.
I(adosh, D. and Struhl,
K.
(1997).
Repression
by
Ume6
involves
recruitment
of a complex
con-
taining Sin3
corepressor
and
Rpd3 histone
deacetylase
to target
promoters. Cell 89'
365-)7 r.
Schreiber-Agus,
N.,
Chin,
L.,
Chen,
K., Torres,
R.,
Rao, G., Guida,
P, Skoultchi,
A.
I., and
DePinho,
R. A.
(1995).
An
amino-terminal
domain of
Mxil
mediates
anti-Myc
oncogenic
activity and
interacts
with
a homolog
of
the
yeast
transcriptional
repressor
SIN3'
Cel/
80,
777-786.
Methytation
of
Histones
and
DNA
Is Con
nected
Reviews
Bannister,
A. J., and
I(ouzarides,
T.
(2005). Revers-
ing histone
methylation.
Nature
436,
r 103-t 106.
Richards,
E. J., Elgin,
S. C.,
and
Richards,
S. C.
(2002\
. Epigenetic
codes
{or heterochromatin
formation
and
silencing:
rounding
up the
usual suspects.
Cell
108,489-500.
Zlnang,
Y. and Reinberg,
D.
(2001).
Tianscription
regulation
by
histone
methylation:
interplay
between
different
covalent
modifications
of
the core
histone
tails.
Genes
Dev.
15,
234)-2360.
References
815
Resea rc
h
Cuthbert,
G. L., Daujat,
S., Snowden,
A. W.,
Erdjument-Bromage,
H., Hagiwara,
T.,
Yamada,
M.,
Schneider, R.,
Gregory, P. D.,
Tempst,
P., Bannister,
A. J., and I(ouzarides,
T.
(20041.
Histone
deimination
antagonizes
argi-
nine
methylatron.
Cell l18, 54r-553.
Fuks, F.,
Hurd, P.
J., Wolf, D.,
Nan, X., Bird,
A. P..
and I(ouzarides,
T.
(2003).
The methyl-CpG-
binding
protein
McCP2 links
DNA merhyla-
tion to histone
methylation.
J Biol.
Chem.278,
4035-4040.
Gendrel, A.
V, Lippman,Z.,Yordan,
C., Colot,
V
and
Martienssen,
R. A.
(20021.
Dependence
of
heterochromatic
histone
H3 methylation pat-
terns
on the Arabidopni
gene
DDMI
. Science
297, t87t-187).
Johnson,
L.,
Cao, X., and
Jacobsen,
S.
(2002).
Interplay
between
two epigenetic
marks. DNA
methylation
and
histone
H3
lysine 9 methyla-
Iion. Curr. Biol.
12, 1360-1367.
Lawrence,
R.
J., Earley, K., Pontes,
O., Silva, M.,
Chen, Z
J., Neves,
N., Viegas,
W., and Pikaard,
C. S.
(2004).
A concerted
DNA
methylation/histone
methylarion
switch regu-
lates
rRNA
gene
dosage
control
and nucleolar
dominance.
MoL
Cell 8,599-609.
Ng,
H.
H., Feng,
Q.,
Wang,
H., Erdjument-
Bromage,
H., Tempst,
P., Zhang,
Y., and
Struhl,
K.
(2002).
Lysine
methylation
within
the
globular
domain
of histone
H3 by Dotl
is
important
for
telomeric silencing
and
Sir
pro-
tein association.
Genes Dev. 16,
I518-1527.
Rea,
S., Eisenhaber,
F.,
O'Carroll,
D.,
Strahl, B. D,.
Sun, Z.
W.,
Sun, M., Opravil,
S., Mechtler,
I(.,
Ponting,
C. P., Allis,
C. D.,
and Jenuwein,
T.
(2000).
Regulation
of chromatin
structure
by
site-specific
histone
H3 methyltransferases.
Nature
406.593-599.
Shi, Y., Lan,
F., Matson,
C., Mulligan,
P.,
Whetstine,
J.
R.,
Cole, P
A., and
Casero,
R. A.
(2004).
Histone
demethylation
mediated
by the nuclear
amine
oxidase
homolog
LSD I.
Cell
119,941-953.
Tamaru,
H.
and
Selker, E.
U.
(2001).
A histone
H3
methyltransferase
controls
DNA
methylation
in Neurospora
crassL.
Nature
414,277-283.
Tamaru,
H.,Zhang,
X.,
McMillen,
D.,
Singh,
p.
B.,
Nakayama,
J., Grewal,
S. I., Allis,
C.
D.,
Cheng,
X., and
Selker, E.
U.
(2003).
Trimeth-
ylated
lysine 9
of histone
H3 is
a mark for
DNA
methylalion
in
Neurosport
crassa
Nat
Genet
34,75-79.
Wang,
Y.,
Wysocka,
J., Sayegh,
J., Lee,
Y. H., Per-
lin,
J. R., Leonelli,
L.,
Sonbuchner,
L.
S.,
McDonald,
C. H., Cook,
R.
G., Dou, Y..
et al.
(20041.
Human PAD4 regulates
histone
argi-
nine
methylation levels
via demethylimina-
tion. Science )06, 279-283.
R esea
rc
h
Resea rc h
Promoter
Activation
Involves
an
0rdered Series of Events
Review
Orphanides,
G. and Reinberg, D.
(2000).
RNA
polymerase
II elongation
through
chromatin.
Nature 407
,
47 l-47 5.
Resea
rc h
Bortvin,
A. and
Winston, F.
(1996).
Evidence
that
Spt6p controls chromatin
structure
by a direct
interaction
with
histones.
Science
272,
t473-1476.
Cosma, M. P., Tanaka,
T., and
Nasmyth, K.
(1999).
Ordered recruitment
of transcription
and
chromatin remodeling
factors
to a
cell cycle
and
developmentally regulated promoter.
Cell
97,299-jtt.
Hassan,
A. H., Neely,
I(. E., and
Workman,
J. L.
(2001
).
Histone
acetyltransferase
complexes
stabilize swi/snf
binding
to
promoter
nucleo-
somes.
Cell
104,
817-827.
Orphanides,
G., LeRoy,
G., Chang,
C. H., Luse,
D.
S., and Reinberg,
D.
(1998).
FACT
a
factor
that facilitates
transcript
elongation
through
nucleosomes.
Cell
92,
105-l16.
Wada, T., Takagi,
T., Yamaguchi,
Y., Ferdous,
A
,
Imai, T.,
Hirose,
S., Sugimoto,
S., Yano, I(.,
Hartzog,
G. A.,
Winston, F., Buratowski,
S.,
and Handa,
H.
(1998).
DSIF,
a novel
transcrip-
tion elongation factor
that regulates
RNA
polymerase
II
processivity,
is composed
of
human
Spt4
and Spt5 homologs.
Genes Dey.
12.34)-356.
Histone Phosphorytation
Affects
Chromatin
Structure
Wang, Y.,
Zhang,
W., Jin, Y.,
Johansen,
J., and
Johansen,
K. M.
(2001).
The
JIL-l
randem
kinase
mediates histone
H3
phosphorylation
and is required
for maintenance
of
chromatin
structure in Drosophila-
Cell 105, 4)3-44).
Some Common Motifs
Are Found
in Proteins
That Modifv
Chromatin
Dhalluin,
C., Carlson,
J.E.,Zeng,L.,He,
C., Aggar-
wal, A. I(.,
and Zhou,
M. M.
(1999).
Srructure
and ligand
of
a
histone
acetyltransferase
bromo
domain.
Nature
399, 491-496.
816
CHAPTER
30 Controlling
Chromatin
Structure
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Epigenetic Effects
Can Be Inherited
.
Epigenetic effects
can
result
from modifi-
cation of a nucleic
acid after it has been
synthesized
or by the
perpetuation
of
pro-
tein structures.
Yeast Prions
Show Unusual Inheritance
o
The
5up35
protein
in its wild-type
sotubte
form is
a termination factor for
tra
nstati
o
n,
.
It can also exist in an
atternative
form
of
otigomeric aggregates, in which it is not
actjve
in
protein
synthesis.
o
The
presence
of the oligomeric
form
causes
newty
synthesized
protein
to
acquire
the inactive
structure.
.
Conversion between
the two
forms is
inftuenced
by chaperones.
o
The witd-type form
has the recessive
genetic
state
psr
and the mutant form has
the dominant
genetic
state PSf+.
Prions Cause
Diseases
in Mamma[s
.
The
protein
responsibte
for scrapie
exists
jn
two forms: the
witd-type
noninfectious
form PrPc, which
is susceptibte
to
pro-
teases,
and the disease-causing
form
PrPs., which
is resistant to
proteases.
r
The neurotogicaI
disease
can be transmit-
ted
to mice by
injecting
the
purified
PrPsc
protein
into
mice.
.
The
recipient
mouse must
have a copy of
the
PrP
gene
coding
for the mouse
p
rotei n.
r
The PrPsc
protein
can
perpetuate itsetf by
causing
the newly
synthesized
PrP
protein
to take
up the
PrPsc
form instead of
the
PrPc
form.
r
Multipte strains
of PrPsc
may
have differ-
ent conformations
of the
protein.
Summary
Introduction
.
Ep'igenetic effects can result from modification of
a nucteic acid after
it
has been synthesized or by
the
perpetuation
of
protein
structures.
Epigenetic inheritance describes the ability of
different states, which
may have
different
phe-
notypic consequences, to be inherited without
any change
in
the sequence of DNA.
This means
that two individuals with the same DNA
sequence
at the locus that controls the effect
may show different
phenotypes.
The
basic cause
of this
phenomenon
is the existence of a self-
perpetuating
structure
in
one of the
individu-
als that does
not
depend on DNA sequence.
Several
different types of structures have the
ability to sustain epigenetic effects:
.
A covalent modification of DNA
(methy-
Iation of a base).
.
A
proteinaceous
structure that assembies
on
DNA.
.
A
protein
aggregare
that controls
the
conformation of new subunits as they
are
synthesized.
In each case the epigenetic state
results from
a difference
in function
(typically
inactivation)
that
is determined by the structure.
In
the
case of DNA methylation, a
meth-
ylated
DNA sequence
may fail
to be transcribed,
whereas
the nonmethylated sequence will be
expressed.
,
.i:
.
'r
'r
:
shows how this situation
is inherited. One
allele has a sequence that
is
methylated
on both strands of DNA, whereas
the other
allele has an unmethvlated secuence.
Replication of
the methylated
allele
creates
hemimethylated daughters
that
are
restored
to the methylated
state
by
a constitutively
active
methylase enzyme.
Replication
does
not
affect the state
of the
nonmethylated
allele.
If
the state of
methylation
affects
transcription,
the two
alleles
differ
in their
state
of
gene
r
il.iiiii
:r, I
,
i Replication
of a
methylated
site
produces
hemimethyiated
DNA, in
which onl"y
the
parental
strand
is
methyl.ated. A
perpetuation methytase
recognizes
hemimeth-
ytated
sites and
adds a
methyl
group
to the
base on
the
daughter strand.
This restores
the
originaI
situation.
in
which the site
is methylated
on
both strands'
A nonmethy-
Lated site
remains
nonmethytated
after
reptication.
31.1
Introduction
819
expression,
even though
their sequences
are
identical.
Self-perpetuating
structures
that assemble
on DNA
usually have
a
repressive
effect
by form-
ing
heterochromatic
regions
that
prevent
the
expression
of
genes
within them.
Their
perpet-
uation depends
on the
ability of
proteins
in a
heterochromatic
region
to remain
bound to
those regions
after replication,
and then
to
recruit
more
protein
subunits
to
sustain the
complex.
If individual
subunits
are distributed
at random
to
each daughter
duplex at replica-
tion, the
two daughters
will
continue to be
marked
by the
protein,
although
its
density will
be reduced
to half
of the level
before replica-
tion.
shows that
the existence
of eni-
genetic
effects forces
us to
the
view
that
a
protein
responsible
for such a
situation must
have some
sort of
self-templating
or self-assembling
capac-
ity to restore
the original
complex.
It can
be the state
of
protein
modification,
rather
than
the
presence
of the
protein per
se,
that is responsible
for
an epigenetic
effect.
Usu-
ally
the tails
of histones H3
and H4
are not acer-
ylated
in
constitutive
heterochromatin.
If
centromeric
heterochromatin
is
acetylated,
though,
silenced
genes
may
become active.
The
effect may
be
perpetuated
through mitosis
and
']r
.r':'
Heterochromatin
is
created
by
proteins
that
associate
with histones.
Perpetuation
through
division requires
that the
proteins
associate
wjth
each
daughter
duptex
and
then recruit
new
subunits
to reassembte
the repressive
c0m
plexes.
meiosis,
which suggests that
an epigenetic
effect
has
been created
by changing
the state of his-
tone acetylation.
Independent
protein
aggregates
that cause
epigenetic effects
(called
prions)
work by
sequestering
the
protein
in a form
in which its
normal function
cannot
be displayed.
Once the
protein
aggregale has
formed, it
forces newly
synthesized
protein
subunits
to
join
it in
the
inactive
conformation.
Heterochromatin
Propagates
from
a
Nucleation
Event
r
Heterochromatin
is nucteated
at
a specific
sequence and
the
inactive
structure
propagates
along the chromatin fiber.
.
Genes within regions
of heterochromatin
are
inactivated.
r
The
length of the inactive region
varies from
ce[[
to cet[
as a
resutt,
inactivation
of
genes
in
this
vicinity
causes
position
effect variegation.
.
Simitar
spreading effects occur
at tetomeres
and at
the sitent
cassettes in
yeast
mating
type.
An interphase
nucleus
contains
both euchro-
matin
and heterochromatin.
The
condensatit_rn
state of heterochromatin
is
close
to that
of
mitotic chromosomes.
Heterochromatin
is inert.
It remains
condensed in interphase,
is transcrip-
tionally repressed,
replicates
late
in S
phase,
and
may be localized
to the nuclear periphery.
C entromeric
heterochromatin
typically
consists
of
satellite DNAs; however,
the formation
of
heterochromatin
is
not rigorously
defined
by
sequence.
When
a
gene
is transferred,
either
by a chromosomal
translocation
or by transfec-
tion and
integration, into
a
position
adjacent
to
heterochromatin,
it maybecome
inactive
as
the
result
of its new location,
implying
that it has
become heterochromatic.
Such inactivation
is the result
of an epige-
netic
effect
(see
Section
31.10,
Epigenetic
Effects
Can Be
Inherited).
It may
differ
between
individual
cells in
an animal,
and results
in
the
phenomenon
of
position
effect
variegation
(PEV),
in which
genetically
identical
cells
have
different phenotypes.
This
has been well
char-
acterized
in Drosophila.
ijl",L.rr'.-!i.
,:;
!,:.
shows
an
example
of
position
effect
variegation
in
the fly
eye. Some
of the regions
in the
eye lack
color,
820 CHAPTER
31 Epigenetic
Effects
Are Inherited