figure 1. caron s & huaman samanez c
DESCRIPTION
Vehicle. Vehicle. Vehicle. Vehicle. Vehicle. WAY362450. CDCA. GW4064. INT-747. GW4064. **. ChREBP-Mlx. HNF4 . ChORE. DR-1. -144. -125. -169. L4. L3. (L4L3) region of the L-PK promoter. F. F. RF. RF. RF + INT-747. RF + INT-747. ***. **. *. **. ***. 25. ***. ***. - PowerPoint PPT PresentationTRANSCRIPT
Figure 1. Caron S & Huaman Samanez C
D
(L4L3) region of the L-PK promoter
ChREBP-Mlx
ChORE
L4 L3-169 -144 -125
DR-1
HNF4
A
Glc
Rel
ati
ve
(L-P
K/3
6B
4)
mR
NA
le
ve
ls
B
Rel
ativ
e (L
-PK
/36B
4)m
RN
A le
vels
0
5
10
15
20
25
30
35
Low High Low High- +
GlcsiRNA FXR - +
***** ***
VehicleGW4064
FXR
-siRNAFXR
+
E****
Rel
ativ
e lu
cife
rase
act
ivit
y
GW4064Glc Low High
- +-High
Low High
VehicleCDCA
******
C
Pla
sma
glu
cose
(m
g/d
l)
F RF RF +INT-747
0
1
2
3
4
5
Rel
ativ
e (L
-PK
/28S
)m
RN
A le
vels
*** **
0
50
100
150
200 **
**
F RF RF +INT-747
0
5
10
15
20
25VehicleGW4064
****
Low High
VehicleWAY362450
*** **
Low High
VehicleINT-747
*** **
Low High
Glc
Rel
ati
ve
(L-P
K/3
6B
4)
mR
NA
le
ve
ls
Actin
1.0 0.6
Figure 2. Caron S & Huaman Samanez C
GW4064
WB : ChREBP
WB : FXR
1 2 3 4 5
- - + - +
95 kDa
59 kDa
IP : FXR AB1 AB2
B
D
ChREBP
Lamin A/C
Low- -
High
GW4064
Glc
1 2 3 4
+ +
95 kDa
67 kDa
A
C
GST GST-FXR
ChREBP
- - +
Mlx
HNF4
Input20%GW4064
FXR fragments
F1-105
F106-196
F197-284
F215-300
F301-384
F215-472
Full length FXR
1 105
AF-1 DBD LBD1 124 196 241 472
106 196
197 284
215 300
301 384
215 472
GST GST-FXR- - +
Input20% GW4064
ChREBP
ChREBP
ChREBP
ChREBP
ChREBP
ChREBP
1 2 3 4
1 2 3 4
Figure 3. Caron S & Huaman Samanez C
Rel
ativ
e L
-PK
p
rom
ote
r o
ccu
pan
cy
ChREBP
Low HighGlc High- -GW4064 +
*** **
Rel
ativ
e L
-PK
p
rom
ote
r o
ccu
pan
cy
HNF4
Low HighGlc High- -GW4064 +
*
Rel
ativ
e L
-PK
p
rom
ote
r o
ccu
pan
cy
FXR
Low HighGlc High- -GW4064 +
Figure 4. Caron S & Huaman Samanez C
B
C
E F
D
GST GST-SMRT
FXR
- - +
1 2 3 4
Input10%GW4064
A
Low High Low HighSi SMRT
Rel
ativ
e (L
-PK
/36B
4) m
RN
A le
vels
- +Glc
- +
VehicleGW4064** **
5
10
15
20
25
30
35
40
***
2
4
6
8
10
12
14
Rel
ativ
e (L
-PK
/36B
4)
mR
NA
leve
ls
Low High Low HighTSAGlc
- +- +
VehicleGW4064
***
***
**
SMRT
-siRNASMRT
+
1.0 0.4
Rel
ativ
e L
-PK
p
rom
ote
r o
ccu
pan
cy
p300
Low HighGlc High- -GW4064 +
* **
Rel
ativ
e L
-PK
p
rom
ote
r o
ccu
pan
cy
CBP
Low HighGlc High- -GW4064 +
*
Rel
ativ
e L
-PK
p
rom
ote
r o
ccu
pan
cy
SMRT
Low HighGlc High- -GW4064 +
*
Rel
ativ
eL-P
K
pro
mo
ter
occ
up
ancy
H3K9-Ac
Low HighGlc High- -GW4064 +
*
Actin
*
Figure 5. Caron S & Huaman Samanez C
AFAS
0
2
4
6
8ApoCIII
Rel
ativ
e m
RN
A
leve
lsLow HighGlc
0.0
0.5
1.0
1.5
2.0
0.0
0.5
1.0
1.5
2.0
2.5PNPLA3 TxNIP
Low High0
5
10
15
20
Low HighGlc
VehicleGW4064
Rel
ativ
e m
RN
A
leve
ls
BChREBP
Rel
ati
ve
Tx
NIP
p
rom
ote
r o
ccu
pa
nc
y
0
20
40
60
0
1
2
3
4
5 FXR
0
2
4
6
8
10 SMRT
Rel
ati
ve
Tx
NIP
p
rom
ote
r o
ccu
pa
nc
y
0
2
4
6
8H3K9-Ac
Low High
GlcGW4064
Low High High- + +
Low High High- + +
02468
101214 p300
Rel
ati
ve
Tx
NIP
p
rom
ote
r o
ccu
pa
nc
y
0
1
2
3
4
5
6 CBP
GlcGW4064
Low High High- + +
Low High High- + +
GlcGW4064
Low High High- + +
Low High High- + +
* * *** *
* * ** *
Figure 6. Caron S & Huaman Samanez C
0.0
0.5
1.0
1.5
2.0
2.5
Low HighGlc
9
012345678
Low HighGlc
0.0
0.51.0
1.5
2.0
2.53.0
3.5
Low HighGlc
0.0
0.5
1.0
1.5
2.0
2.5
Low HighGlc
0.0
0.51.0
1.5
2.0
2.5
3.0
3.5
Low HighGlc
0.0
0.51.0
1.5
2.0
2.53.0
3.5
Low HighGlc
PGM1HK3
TPI1 PGAM1
ACSS1 LDHA
Rel
ativ
e m
RN
A
leve
lsR
elat
ive
mR
NA
le
vels
Rel
ativ
e m
RN
A
leve
ls
VehicleGW4064
** * ** *
** * * *
* * *** *
Figure 7. Caron S & Huaman Samanez C
L-PK promoter
ChREBP
ChORE
L4 L3-169 -144 -125
DR1
HNF4p300 CBPFXR
High glucose
L-PK promoter
ChREBP
ChORE
L4 L3-169 -144 -125
DR1
HNF4
p300
CBP
FXR
High glucose + FXR activation
SMRT
A
BHDAC
histones
Ac
histones
Ac