e. lephant ? e. colimcb.berkeley.edu/courses/mcb140/syllabus/urnov_lectures/epi1.pdf · 5 17 mcb...
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1
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E. c
oli=
E. l
epha
nt ?
F. J
acob
J. M
onod
A. P
arde
e
D. H
awth
orne
H. D
ougl
asY.
Osh
ima
1965
1966
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Ana
logy
and
hom
olog
y as
tool
s in
ge
netic
inve
stig
atio
n
Sta
pes
Incu
sM
alle
usM
amm
alS
tape
sQ
uadr
ate
(bon
e)A
rticu
lar (
bone
)A
mph
ibia
n
Hyo
man
dibu
lar
carti
liage
Pal
atoq
uadr
ate
carti
lage
Mec
kel's
car
tilag
eS
hark
Hyo
id A
rch
(dor
sal)
Man
dibu
lar A
rch
(dor
sal)
Man
dibu
lar A
rch
(ven
tral)
Ani
mal
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a ce
lls p
rodu
ce a
pher
omon
e an
d α
rece
ptor
αce
lls p
rodu
ce α
pher
omon
e an
d a
rece
ptor
dipl
oid
(a/α
) cel
ls p
rodu
ce n
one
of th
e ab
ove
2
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Shm
ooA
l Cap
p (1
948)
–Li
’l A
bner
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Mar
sh a
nd R
ose
diag
ram
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The
phen
otyp
e of
a h
aplo
id y
east
cel
l with
re
spec
t to
mat
ing
is d
eter
min
ed b
y tra
nscr
iptio
n fa
ctor
s
An α
cell
prod
uces
two
trans
crip
tion
fact
ors,
M
atα
1p a
nd M
atα
2p, t
hat e
nsur
e ex
pres
sion
of
αsp
ecifi
c ge
nes,
incl
udin
g th
e ph
erom
one
and
rece
ptor
, and
repr
ess
expr
essi
on o
f asp
ecifi
c ge
nes.
In a
n a
cell,
Matα
1p a
nd M
atα
2p a
re n
ot
expr
esse
d, a
nd a
diff
eren
t tra
nscr
iptio
n fa
ctor
is
expr
esse
d, M
ata1
p. T
he α
gene
s ar
e of
f, an
d th
e a
gene
s (p
hero
mon
e an
d re
cept
or) a
re o
n.
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A.9
3
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Am
azin
g bu
t tru
e
A w
ild-ty
pe h
aplo
id y
east
cel
l con
tain
s TH
RE
E
copi
es o
f mat
ing
type
-det
erm
inin
g ge
nes:
•C
opy
#1: t
he α
1 an
d α
2 ge
nes
(sile
nt).
•C
opy
#2: t
he a
1an
d a2
gene
s (a
lso
sile
nt).
•C
opy
#3: A
n ad
ditio
nal c
opy
of g
enes
in it
em 1
, or
of th
e ge
nes
in it
em 2
, but
act
ive.
Whi
chev
er g
enes
are
con
tain
ed in
cop
y #3
de
term
ines
the
mat
ing
type
.
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A.1
1
A.1
2
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“An
easi
ly u
nder
stoo
d, w
orka
ble
fals
ehoo
d is
mor
e us
eful
than
an
inco
mpr
ehen
sibl
e tru
th.”
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cen
MA
TH
MLα
HM
Ra
α1
α2
a1a2
αce
ll
α1
α2 ac
tive
sile
ntsi
lent
4
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Loss
of s
ilenc
ing
at th
e si
lent
mat
ing
type
ca
sset
tes
crea
tes
a “n
onm
ater
” –a
hapl
oid
that
is a
/αan
d th
at th
inks
it’s
a d
iplo
id.
cen
MA
TH
MLα
HM
Ra
α1
α2
a1a2
αce
ll
α1
α2 ac
tive
activ
eac
tive
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Scr
een
for s
ilenc
ing
mut
ants
A s
ampl
e “s
cree
n”:
1.Ta
ke h
aplo
id c
ells
.2.
Mut
ate
them
.3.
Scr
een
for t
hose
that
don
’t m
ate.
Pro
blem
: mat
ing
is s
o m
uch
mor
e th
an
prop
er s
ilenc
ing
of m
atin
g ty
pe lo
ci!!
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The
mat
ing
pher
omon
e re
spon
se
Jere
my
Thor
ner
Thor
ner d
iagr
amA
lso
see
Fig.
A.1
3.
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How
to s
cree
n fo
r sile
ncin
g m
utan
ts
cen
MA
TH
MLα
HM
Ra
α1
α2
a1a2
ace
ll
a1a2 ac
tive
sile
ntsi
lent
Jasp
er R
ine
and
Ira H
ersk
owitz
(198
7) G
enet
ics
116:
9-22
.
5
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How
to s
cree
n fo
r sile
ncin
g m
utan
ts
cen
mat
a1-1
HM
Lαα1
α2
a1a2 ac
tive
sile
ntsi
lent
Jasp
er R
ine
and
Ira H
ersk
owitz
(198
7) G
enet
ics
116:
9-22
.
HM
Lαα1
α2
Not
e: m
ata1
-1 is
a s
peci
al a
llele
of t
he a
gene
–it
is re
cess
ive
to α
18M
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sper
Rin
e an
d Ira
Her
skow
itz (1
987)
Gen
etic
s 11
6: 9-
22.
Rin
e sc
hem
atic
mat
e to
ace
lls
19M
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The
data
•C
olon
ies
scre
ened
: 675
,000
•C
olon
ies
that
mat
ed to
a: 2
95•
Maj
or c
ompl
emen
tatio
n gr
oups
: 4
sile
nt in
form
atio
n re
gula
tors
:
SIR
1, S
IR2,
SIR
3, S
IR4
Jasp
er R
ine
and
Ira H
ersk
owitz
(198
7) G
enet
ics
116:
9-22
.20
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Que
stio
n
Wha
t mol
ecul
ar m
echa
nism
s ar
e re
spon
sibl
e fo
r si
lenc
ing
at th
e m
atin
g ty
pe lo
ci?
→he
tero
chro
mat
in fo
rmat
ion
in m
etaz
oa→
pros
tate
can
cer
→br
east
can
cer
→ag
eing
→“n
orm
al”g
ene
regu
latio
n in
mam
mal
s
6
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Hom
ewor
k
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How
can
one
exp
lain
the
evol
utio
n of
two
dist
inct
mat
ing
type
s in
bud
ding
yea
st?
Sur
ely
a pa
thw
ay c
ould
hav
e ju
st
evol
ved
for t
he fu
sion
of t
wo
iden
tical
hap
loid
cel
ls?
23M
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Two
mat
ing
type
s ha
ve e
volv
ed u
nder
se
lect
ive
pres
sure
to a
void
inbr
eedi
ng
M
D1
D2
D1
D2
One
evo
lutio
nary
adv
anta
ge o
f mat
ing
is th
e pr
oduc
tion
of n
ovel
gen
otyp
ic c
ombi
natio
ns v
ia th
e fu
sion
of t
wo
geno
mes
with
diff
eren
t life
his
torie
s.
x
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Gra
ndda
ught
ers
of a
ny g
iven
m
othe
r can
sw
itch
mat
ing
type
7
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urno
v@be
rkel
ey.e
du
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cen
MA
TH
MLα
HM
Ra
α1
α2
a1a2
αce
ll
α1
α2
cen
MA
TH
MLα
HM
Ra
α1
α2
a1a2
ace
ll
a1a2ac
tive
sile
ntsi
lent
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Epi
gene
tic in
herit
ance
•In
an α
stra
in, t
he g
enet
ic in
form
atio
n at
MA
T an
d at
HM
L αis
iden
tical
.•
The
one
at M
AT
is e
xpre
ssed
, but
the
one
at
HM
L is
not
–it
is e
pige
netic
ally
sile
nced
.
Epi
gene
tic: m
itotic
ally
sta
ble
(per
sist
s th
roug
h ce
ll di
visi
on) c
hang
e in
gen
e ex
pres
sion
sta
te th
at is
no
t ass
ocia
ted
with
a c
hang
e in
DN
A s
eque
nce.
Exa
mpl
es: X
chr
omos
ome
inac
tivat
ion;
impr
inte
d ge
nes;
tran
sgen
e si
lenc
ing
in g
ene
ther
apy.
8
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> 1
met
re<
10-5 m
etre
s
15,0
00x
com
pact
ion
Com
pact
ion
into
chr
omat
in b
rings
th
e eu
kary
otic
gen
ome
to li
fe
30M
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“Bea
ds o
n a
strin
g”
31M
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The
Nuc
leos
ome
Cor
e P
artic
le:
8 hi
ston
es, 1
46 b
p of
DN
A
32M
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His
tone
s:C
onse
rved
and
C
harg
ed
H.s
.= L
ycop
ersi
con
escu
lent
um
9
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“Ext
rem
ely
cons
erve
d hi
ston
e H
4 N
term
inus
is
disp
ensa
ble
for g
row
th b
ut e
ssen
tial f
or re
pres
sing
th
e si
lent
mat
ing
loci
in y
east
” (M
. Gru
nste
in)
Kay
ne e
t al.
(198
8) C
ell 5
5: 2
7-39
.
Fig.
3 k
ayne
35M
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6K
ayne
et a
l. (1
988)
Cel
l 55:
27-
39.
Fig.
6 a
nd 7
of K
ayne
.
36M
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6K
ayne
et a
l. (1
988)
Cel
l 55:
27-
39.
10
37M
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Ace
tyla
tion
of ly
sine
in h
isto
ne ta
il ne
utra
lizes
its
char
ge (1
964)
38M
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“Gen
etic
evi
denc
e fo
r an
inte
ract
ion
betw
een
SIR
3 an
d hi
ston
e H
4 in
the
repr
essi
on o
f the
sile
nt
mat
ing
loci
in S
acch
arom
yces
cer
evis
iae”
John
son
et a
l. (1
990)
PN
AS
87:
6286-
6290
.
Rev
erse
gen
etic
s: in
trodu
ce p
oint
mut
atio
ns in
H4
tail!
!
39M
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6Jo
hnso
n et
al.
(199
0) P
NA
S 8
7:62
86-62
90.
Tabl
e 2
40M
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11
41M
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And
5 y
ears
late
r …
Sir3
p an
d S
ir4p
bind
H3
and
H4
tails
Hec
ht e
t al.
(199
5) C
ell 8
0: 5
83.
42M
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Hou
ston
, we
have
a …
Eve
ry n
ucle
osom
e in
the
cell
has
an H
3 an
d H
4 ta
il (tw
o of
eac
h, a
ctua
lly).
Why
do
the
SIR
s bi
nd o
nly
whe
re th
ey b
ind?
43M
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The
sile
ncer
s
“Haw
thor
ne d
elet
ion”
(196
3) a
nd o
nwar
ds:
two
sile
ncer
s fla
nk th
e m
atin
g ty
pe lo
ci:
44M
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The
key
ques
tion
How
do
the
SIR
s sp
read
from
the
sile
ncer
and
ove
r the
m
atin
g ty
pe lo
ci
gene
s?
= ho
w d
o th
e S
IRs
actu
ally
sile
nce
txn?
12
45M
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Roy
Fry
e (P
itt)
“Cha
ract
eriz
atio
n of
five
hum
an c
DN
As
with
hom
olog
y to
th
e ye
ast S
IR2
gene
: Sir2
-like
pro
tein
s (s
irtui
ns)
met
abol
ize
NA
D a
nd m
ay h
ave
prot
ein
AD
P-
ribos
yltra
nsfe
rase
act
ivity
” BB
RC
260
: 273
(199
9).
1. B
acte
ria h
ave
prot
eins
hom
olog
ous
to S
ir2.
2. S
o do
hum
ans
(>5)
.
3. T
he b
acte
rial p
rote
ins
are
enzy
mes
, and
use
NA
D to
A
DP
-rib
osyl
ate
othe
r pro
tein
s.
46M
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J. D
enu:
Sir2
p is
a N
AD
-dep
ende
nthi
ston
e de
acet
ylas
e (H
DA
C)
Tann
er e
t al.,
PN
AS
97:
141
78 (2
000)
Sir2
p
47M
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usch
e L,
Kirc
hmai
er A
, Rin
e J
(200
2) M
ol. B
iol.
Cel
l 13:
220
7.48
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acet
ylat
ion
His
tone
tail
acet
ylat
ion
prom
otes
ch
rom
atin
unf
oldi
ng (s
omeh
ow)
13
49M
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Nex
t tim
e:
the
gene
tics
of h
eter
ochr
omat
in
in m
etaz
oa