Biology Reference
In-Depth Information
MIE promoter at late times, it was proposed that IE86 mediated the changes in the
chromatin structure (Reeves et al. 2006). During latency, the HCMV MIE promoter
is also associated with repressive chromatin (Reeves et al. 2005). The chromatin
associated with the MIE promoter during latency and reactivation are reviewed (see
the chapter by
Μ
. Reeves and J. Sinclair, this volume).
Transcription from Viral and Cellular Promoters
Viral Promoters
A strong heterochromatin structure forms quickly on the HCMV genome in
nonpermissive, undifferentiated cells (Reeves et al. 2005; Ioudinkova et al. 2006;
Yee et al. 2007). The transcriptional repressors may cause a closed viral chromatin
structure (see the chapter by
. Reeves and J. Sinclair, this volume). The MIE
promoter is repressed by heterochromatin, and consequently there is no expression
of the MIE proteins. The IE86 protein is a master regulator of HCMV transcrip-
tion required for early viral gene expression. The IE72 protein augments the activ-
ity of the IE86 protein by inhibiting histone deacetylase activity (Tang and Maul
2003; Nevels et al. 2004). Early viral gene expression from the viral genome in a
latently infected cell, such as HCMV-infected undifferentiated THP-1 cells or
murine CMV-infected mice, requires the expression of both of the MIE proteins
(Kurz et al. 1999; Kurz and Reddehase 1999; Yee et al. 2007). Nevertheless, this
is not sufficient to reactivate virus replication without cellular differentiation.
Cellular factors induced or reduced by cellular differentiation appear to be critical
for viral DNA replication and production of infectious virus (Murphy et al. 2002;
Reeves et al. 2005). Therefore, sporadic expression of the MIE genes may occur,
but it is not always sufficient to signal viral reactivation and replication.
The IE86 protein transactivates early viral promoters by interacting with cellular
basal transcription machinery and requires a TATA box-containing promoter to
transactivate downstream transcription (Lukac et al. 1994). Figure 2a shows the
broad regions of the IE86 protein that interact with the basal transcription machinery
and Table 1 summarizes the number of mutations in this region. Truncated forms of
the IE86 protein interact in vitro with TBP, TFIIB, and TAFII130/TAF4 and the
IE86 protein rescues defective TAFII250 (Caswell et al. 1993; Lukac et al. 1994,
1997). Other cellular transcription factors and chromatin remodeling proteins also
interact and contribute to the activity of the IE86 protein such as CREB, SP1, Tef-1,
Egr-1, p300/CBP, and P/CAF (Lukac et al. 1994; Sommer et al. 1994; Lang et al.
1995; Scully et al. 1995; Schwartz et al. 1996; Yoo et al. 1996; Bryant et al. 2000).
Chromatin immunoprecipitation (ChIP) assays demonstrated that TBP is associated
with HCMV early promoters, but activation of the viral promoter requires the pres-
ence of functional IE86 protein (Petrik et al. 2007). IE86 protein attracts histone
acetylases, which are key to activating the early viral promoters (Bryant et al. 2000).
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