Chromatin remodeling complexes regulating HIV1 Transcription and latency

1
Chromatin remodeling complexes regulating HIV-1
Transcription and latency Fatah
Kashanchi, Ph.D. The George Washington
University Medical Center Washington, DC,
USA
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• Topics
• Activation of transcription (Euchromatin, i.e.,
  Tat Acetylation and histone modifications)
• Suppression of transcription (Heterochromatin,
  i.e., Tat Methylation and TAR miRNA)

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Important cis-acting elements on the HIV-1
promoter
-454
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10
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Histone modifications
.RKKRR. Tat
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Mammalian SUV39 family of SET domain containing
HMT
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HIV-1 Produces a Viral miRNA
B)
A)
T-Cell Blasts
- HIV
HIV
MW
No RNA
ACH2
THP-1
OM10.1
HLM-1
Day 6
Day 12
Day 6
Day 12
CEM
Beads Alone
Biotin TAR Beads
ACH2
ACH2
BJAB
BJAB
CEM
293
CEM
293
Dicer


- 27 nt Protection of probe by full length
mRNA - 22 nt Protection of probe by TAR miRNA
D)
C)
Relative Luciferase Expression
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Recruitment of HDAC by TAR miRNA
A)
B)
Transfection of pLTR-Luc
Integrated LTR Luciferase
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Down-regulated genes
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GWUMC Reem Berro Zak Klase Sheng-Hao Chao
Longwen Deng Vincent Lacoste Anne
Pumfery Kaili Wu Shabnam Dadgar Kylene Kehn
Cynthia de La Fuente Anila Seelamgari Madhur
Gupta Maria Bottazzi Howard Florey Institute
University of Melbourne John Wade
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Sequence similarity among p50, p53, ACTR and Tat
426
446

K
K

S
N
A
G
M
H
G
T
M
D
T
E
S
D
E
G
C
K
p50(NF
B)
P
k
M
K
K
K
H
p53

S
H
I
K
S
K
G
Q
S
T
S
R
L
F
K
T
Q
L
L
L
L
H
K
K
K
ACTR

G
A
E
N
T
G
P
L
E
S
K
G
K
K
Tat

V
C
F
M
Q
G
L
G
I
S
Y
G
R
R
Q
R
R
K
R
36
56
Ac
Ac
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