REVIEW ARTICLE
Nuclear actin and actin-binding proteins in the regulation
of transcription and gene expression
Bin Zheng
1
, Mei Han
1
, Michel Bernier
2
and Jin-kun Wen
1
1 Department of Biochemistry and Molecular Biology, Hebei Medical University, Shijiazhuang, China
2 Laboratory of Clinical Investigation, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA
Actin is a major component of the cytoskeleton and
plays a critical role in all eukaryotic cells. The actin
cytoskeleton functions in diverse cellular processes,
including cell motility, contractility, mitosis and cytoki-
nesis, intracellular transport, endocytosis and secretion
[1,2]. In addition to these mechanical functions, actin
has also been implicated in the regulation of gene tran-
scription, through either cytoplasmic changes in cyto-
skeletal actin dynamics [3] or the assembly of
transcriptional regulatory complexes [4]. Cytoskeletal
actin dynamics, i.e. actin polymerization by which
monomeric actin (globular actin or G-actin) is assem-
bled into long actin polymers (filamentous actin or
F-actin) and actin deploymerization by which F-actin
is severed into G-actin, is key for these diverse func-
tions. The dynamic nature of the actin cytoskeleton
is determined spatiotemporally by the actions of
numerous actin-binding proteins (ABPs). The activity

muscle activator of Rho signaling and actin-binding LIM protein regulate
actin dynamics and serum response factor-dependent muscle-specific
gene expression. Functionally and structurally unrelated cytoplasmic ABPs
interact cooperatively with nuclear receptor and regulate its transactiva-
tion. Furthermore, ABPs also participate in the formation of transcription
complexes.
Abbreviations
ABLIM, actin-binding LIM protein; ABP, actin-binding protein; ANF, atrial natriuretic factor; AR, androgen receptor; CARM1, coactivator-
associated arginine methyltransferase 1; CBP, CREB binding protein; DBD, DNA-binding domain; FHL, four and a half LIM domains; FLAP1,
Fli-I LRR-associated protein 1; Fli-I, flightless-1; FLNa, filamin-A; FOXC1, forkhead box C1; GRIP1, glucocorticoid receptor-interacting protein 1;
HAT, histone acetyltransferase; HDAC, histone deacetylase; HF, hydroxyflutamide; hhLIM, human heart LIM protein; hnRNPs, heterogeneous
nuclear ribonucleoproteins; LBD, ligand-binding domain; LEF1 ⁄ TCF, lymphoid enhancer factor ⁄ T-cell factor; LRR, leucine rich repeat; MEF2,
myocyte enhancer factor 2; MRTF, myocardin-related transcription factor; NLS, nuclear localization signals; NM1, nuclear myosin 1; PBX1,
pre-B-cell leukemia transcription factor 1; PCAF, p300 ⁄ CREB binding protein-associated factor; PEBP2b, polyoma enhancer-binding protein;
PIC, pre-initiation complex; Pol I, RNA polymerase I; Pol II, RNA polymerase II; Pol III, RNA polymerase III; RNP, ribonucleoprotein; SRF,
serum response factor; STARS, striated muscle activator of Rho signaling; SV, supervillin; SWI ⁄ SNF, switch ⁄ sucrose nonfermentable complex.
FEBS Journal 276 (2009) 2669–2685 ª 2009 The Authors Journal compilation ª 2009 FEBS 2669
monomer availability. Transcriptional regulation, med-
iated by cytoskeletal actin dynamics, can be attributed
to modulation of the subcellular localization of tran-
scriptional regulators by ABPs [5]. In addition, some
of the mechanisms by which actin affects transcription
and its regulation depend on molecular interactions of
actin with RNA polymerases and components of the
transcription machinery in the nucleus.
The role of actin in transcription and
its regulation
Actin is both a major cytoskeletal component of all
eukaryotic cells and also a constitutent of nuclear pro-
tein complexes. Nuclear actin plays a role in many

the activation of transcription. In addition, actin is
required for the initiation of transcription through par-
ticipation in the formation of PICs [17]. These conclu-
sions are based on the following data: (a) b-actin
participates directly in Pol II transcription, using only
purified transcription factors [18,19]; (b) nascent RNA
molecules are associated with actin in the nuclear
matrix and antibodies to b-actin inhibit the synthesis
of nascent transcripts and Pol II transcription [17,19];
(c) adding actin to a highly purified Pol II fraction
stimulates transcription [19]; (d) actin colocalizes with
transcription sites in early mouse embryos [4,17];
(e) actin is recruited to the promoter region of tran-
scribing genes in vivo [19,20]; (f) antibodies to b-actin
inhibit the production of a 15-nucleotide transcript
that is a prerequisite for the commitment to elongation
[19,21]; (g) actin is a component of pre-mRNP parti-
cles, and is incorporated into pre-mRNAs by binding
to a specific subset of RNA-binding proteins [4,22];
and (h) actin is a component of PICs and depletion of
actin prevents their formation [19,23]. The above
evidence suggests that there is a strong and specific
interaction between actin and Pol II, and actin partici-
pates in Pol II transcription. What then is the function
of actin in Pol II transcription? From the above data,
we conclude that: (a) based on chromatin immunopre-
cipitation assays results, which show that actin is
recruited to genes poised to begin transcribing, it is
known that actin is involved in recruiting Pol II to the
PIC [19]; (b) decreased actin levels resulting from anti-

2670 FEBS Journal 276 (2009) 2669–2685 ª 2009 The Authors Journal compilation ª 2009 FEBS
region when compared with the dissociation of Pol III,
which suggests that b-actin dissociates from the Pol III
complex. Third, many experiments have shown that
b-actin is required for Pol III transcription [27,29,32].
The monomeric form of actin is required for Pol III
transcription, suggesting that b-actin is essential for
basal RNA polymerase transcription.
Actin and NM1 interact with different components
of the RNA polymerase I (Pol I) machinery, and
together serve as a nucleolar motor involved in the
transcription of ribosomal RNA genes [26,33]. Recent
studies have revealed that actin is associated with
rDNA genes, and microinjection of anti-actin Ig into
the nuclei of HeLa cells inhibits pre-rRNA synthesis
in vivo [25,34]. The interaction of NM1 with actin in
the initiation complex may trigger a conformational
change that favors the transition of Pol I from the
initiation phase to the elongation phase [25,33]. NM1
mutants that lack ATPase activity or actin binding are
not capable of associating with Pol I [17], and their
association with rDNA is greatly impaired. Moreover,
the association of actin and NM1 with Pol I is abol-
ished in the presence of ATP and is stabilized by
ADP, further suggesting that nuclear actomyosin com-
plexes act as a molecular motor that facilitates tran-
scription [17]. NM1 binds the DNA backbone via its
positively charged tail domain, whereas the head inter-
acts with actin bound to RNA polymerase [4]. It has
been suggested that by anchoring NM1 to DNA, and

BRG1 ATPase activity, and this interaction is necessary
for binding of the BAF complex to chromatin
[27,29,40]. Actin binding to BRG1 is required for stable
association of the complex and provides a link between
the chromatin-remodeling complex and the nuclear
matrix [5,41]. In the INO80 complex, actin is required
for efficient DNA binding, ATPase activity and nucleo-
some mobilization, as INO80 complexes lacking actin,
as well as the actin-related proteins, ARP4 and ARP8,
are deficient for these activities [15]. BAF53 and b-actin
have also been identified as subunits of the human
TIP60 histone acetyltransferase (HAT) complex, which
is involved in DNA repair and apoptosis, and BAF53 is
found in a distinct HAT complex involved in c-myc
activation, whereas Act3 ⁄ ARP4 and actin are compo-
nents of the yeast Nu4A HAT complex [38,42]. In the
yeast Nu4A HAT complex, actin and Act3 ⁄ ARP4 are
essential for the structural integity and activity of the
complex [38]. The presence of actin in chromatin-
remodeling complexes suggests that there is a functional
link between actin and regulation of the chromatin
structure, and a major function of actin is to act as an
allosteric regulator in the remodeling of some macro-
molecular assemblies, such as chromatin-remodeling
factors or transcription complexes.
Actin serves as a component of RNP
The hnRNP U, a component of pre-mRNP particles,
has been shown to interact directly with actin through
a specific and conserved actin-binding site located in
the hnRNP U C-terminus and associate with the phos-

hnRNP U. Moreover, it has been shown that
actin, hnRNP U and PCAF associate with the Ser2 ⁄ 5-
and Ser2-phosphorylated Pol II C-terminal domain.
hnRNP U and PCAF are present at the promoter and
coding regions of constitutively expressed Pol II genes
and are associated with RNP complexes [13]. In sum-
mary, these finding suggest that actin, HRP65-2 and
HAT (p2D10 or PCAF) are assembled into nascent
pre-mRNPs during transcription. Based on the evi-
dence, it may be proposed that the actin–HRP65-2–
HAT complex is part of the nascent pre-mRNP, and
can travel along the transcribed gene, allowing HAT
to acetylate histones. According to this proposal, the
actin–HRP65-2–HAT complex maintains the chroma-
tin in a transcription-competent conformation. This
model is supported by the observation that H3 acetyla-
tion is reduced and transcription is inhibited when the
interaction between actin and HRP65-2 is disrupted
[22]. In addition, actin-mediated Pol II transcriptional
control may be sensitive to the different polymeriza-
tion states of actin [17]. Transcriptionally competent
actin may be present in a monomeric or oligomeric
form which is different from the canonical actin fila-
ments. The polymerization states of actin involved in
the initiation or elongation phases are different
(Fig. 1) [43].
Roles of ABPs in the regulation of
muscle-specific gene expression
The cytoplasmic dynamics of the actin cytoskeleton
have been shown to regulate the subcellular localiza-

Actin
Actin
mRNA processing
CTD
P
P
P
Pre-mRNA
Ac
Ac
Actin
polymerization
?
Activator
hnRNP U
PCAF or
P2D10
Pol II
HRP65-2
Fig. 1. Model for actin–hnRNP U-mediated control of pol II transcription elongation. Actin may modulate several steps in Pol II transcription
initiation and elongation, either as a monomer or as a polymer. Actin may modulate transcription as a monomeric component of transcription
preinitiation, chromatin-remodeling and hnRNP complexes. During transcription elongation, actin may be recruited to the elongating transcrip-
tion machinery via the hyperphosphorylated C-terminal domain and then to the nascent RNP, where actin in complex with the hnRNP U can
facilitate recruitment of PCAF or P2D10 to the active gene. Formation of actin filaments in the proximity of the Pol II C-terminal domain may
help establish a network of interactions between the various factors necessary for transcription elongation and pre-mRNA processing.
Actin and ABPs in transcription regulation B. Zheng et al.
2672 FEBS Journal 276 (2009) 2669–2685 ª 2009 The Authors Journal compilation ª 2009 FEBS
MRTF-A associates with G-actin, is predominantly
localized in the cytoplasm of NIH 3T3 cells in the
absence of serum and accumulates in the nucleus in

The STARS protein contains 375 amino acids, with
the conserved ABD contained within the C-terminal
142 residues [55]. The STARS C-terminal deletion
mutant, N233, which cannot bind actin or activate
SRF, fails to induce the nuclear accumulation of
MRTF-A and -B. By contrast, the C-terminal 142
amino acids of STARS, which bind actin and stimulate
SRF, induce the nuclear accumulation of MRTFs as
efficiently as full-length STARS. STARS N233 fails to
enhance MRTF-dependent activation of SRF-depen-
dent reporters, whereas STARS C142 synergistically
enhances MRTF-mediated transcription to the same
level as full-length STARS [55]. These results demon-
strate that the ABD of STARS is both necessary and
sufficient for the nuclear accumulation and transcrip-
tional activation of MRTFs by STARS.
The activity of STARS involves actin dynamics.
Treatment of NIH 3T3 cells with latrunculin B, which
sequesters actin monomers and prevents Rho-depen-
dent nuclear accumulation of MRTF-A and SRF
activation [46], blocks the nuclear accumulation
of MRTF-A and -B in the presence of STARS.
Conversely, cytochalasin D, which dimerizes actin, but
prevents actin polymerization and activates SRF,
strongly induces the nuclear translocation of MRTFs,
even in the absence of STARS [54]. Consistent with
these effects on MRTF nuclear import, latrunculin B
significantly blocks the stimulatory effect of STARS
on MRTF-dependent transcription, and cytochala-
sin D enhances the activity of MRTFs alone. These

mulating in the nucleus upon activation of Rho
GTPase signaling, which alters interactions between
G-actin and the RPEL domain. Guettler et al. [57]
showed that the RPEL domain of MRTF-A binds
actin more strongly than the RPEL domain of myocar-
din, and that the RPEL motif itself is an actin-binding
element. RPEL1 and RPEL2 of myocardin bind actin
weakly compared with MRTF-A, whereas RPEL3 is
of comparable and low affinity in the two proteins.
Actin binding by all three motifs is required for
MRTF-A regulation. The differing behaviors of
MRTF-A and myocardin are specified by the RPEL1–
RPEL2 unit, whereas RPEL3 can be exchanged
B. Zheng et al. Actin and ABPs in transcription regulation
FEBS Journal 276 (2009) 2669–2685 ª 2009 The Authors Journal compilation ª 2009 FEBS 2673
between them. It has been proposed that differential
actin occupancy of multiple RPEL motifs regulates
nucleocytoplasmic transport and MRTF-A activity.
Because myocardin is insensitive to the effects of
STARS, its target genes are expected to be highly
active, irrespective of the polymerization state of actin.
However, STARS would be expected to further aug-
ment the expression of these genes via its actions on
MRTF-A and -B, which are also expressed in cardiac
muscle and which form heterodimers with myocardin.
In a yeast two-hybrid screen of a skeletal muscle
cDNA library using STARS as bait, Barrientos et al.
[58] identified two novel members of the actin-binding
LIM protein (ABLIM) family, ABLIM-2 and -3, as
STARS-interacting proteins. These novel proteins con-

contains two essential SRF-binding sites and is highly
sensitive to STARS activity [58]. The data suggest that
ABLIM-2 and -3 stimulate STARS activity. ABLIM-2
and -3 enhance STARS-dependent SRF-transcription
in COS cells in a dose-dependent manner [58], suggest-
ing that STARS and ABLIMs both physically interact
and functionally synergize to deliver activating signals
to SRF. The data imply that, in striated muscle,
STARS plays a critical role in the MRTF-A nuclear
translocation process; STARS promotes the nuclear
translocation of MRTFs, and thereby SRF-dependent
transcription (Fig. 2).
STARS activation of SRF-dependent transcription
is mediated, in part, by a Rho-dependent mechanism,
because the Rho inhibitor C3 transferase reduces SRF
activation by STARS. The ability of the Rho kinase
inhibitor, Y-27632, to diminish SRF activation by
STARS also suggests that Rho kinase is a downstream
effector of STARS [55]. The Rho family of GTPases,
including the best characterized members, Rho, Rac
and Cdc42, serve as molecular switches in the regula-
tion of a wide variety of signal transduction pathways
[61,62], in particular, actin polymerization and stress
fiber formation [63]. RhoA signaling has been shown
to induce the nuclear import of MRTF-A in smooth
muscle cells, thereby triggering smooth muscle gene
activation [64]. It is well-known that actin dynamics
and Rho signaling are involved in STARS-induced
nuclear translocation and transcriptional activation
of MRTFs, and Rho activity is crucial for actin

as cell proliferation, cell growth, differentiation and
cell death [65,66]. The AR contains an N-terminal
domain harboring activation function 1, a central
DNA-binding domain (DBD) and a C-terminal ligand-
binding domain (LBD) containing activation func-
tion 2 [67–70]. Upon binding androgens, the AR LBD
undergoes conformational changes leading to dissocia-
tion from chaperones and translocation to the nucleus
[71–74]. AR binding to DNA facilitates the recruit-
ment of general transcriptional machinery and ancil-
lary factors that result in the activation or repression
of specific genes in targeted cells and tissues [75]. In
the last decade, an increasing number of proteins have
been proposed to possess AR coactivating or core-
pressing characteristics [76,77]. Cofactors facilitate AR
transcription function by histone modifications, chro-
matin remodeling and regulation of the AR N-terminal
domain, and the LBD interaction (N ⁄ C interaction)
[78–82]. All available data suggest that no single
AR-binding protein completely defines the multiple
functions of the AR in controlling cellular growth and
differentiation in normal and malignant cells [75].
Alternatively, AR pleiotropic activities are probably
mediated through its binding to specific functional pro-
tein complexes to carry out its broad biological func-
tions in mammalian cells. More than 200 nuclear
receptor coregulators have been identified since the
first nuclear receptor coactivator, SRC-1, was isolated
in 1995 [83]. Among the nuclear receptor coregulators,
ABPs and actin monomers bind to the AR, indicating

RE
R AR
AR
HSP
AR AR
ABPs
ABPs
Coactivators
HAT
Actin
AR nuclea
translocation
AR N/C
interaction
Coactivator
competition
HDAC chromatin
condensation
Actin
Pol II
ABPs
Fig. 3. Regulation of androgen receptor
gene transcription by actin-binding proteins.
B. Zheng et al. Actin and ABPs in transcription regulation
FEBS Journal 276 (2009) 2669–2685 ª 2009 The Authors Journal compilation ª 2009 FEBS 2675
full-length FLNa releases FLNa(16–24) [86–90]. This
naturally occurring C-terminal 100 kDa fragment of
filamin, interacting with the motor protein dynein,
may exert its inhibitory effect by interfering with inter-
actions between the N- and C-terminal domains, and

Direct or indirect
association
with the AR Region
Gelsolin ()) Actin filament
severing
and capping
protein
Involved in gel-to-sol
transformations;
severs and caps
polymeric actin
filaments; acts in
the actin-scavenging
system; inhibits actin
polymerization
Coactivator Promotes AR
activity in a
ligand-enhanced
manner
Direct LBD
Flightless I NLS Actin-
remodeling
proteins
Possess F-actin-serving
activity
Coactivator Does not enhance
the activity of
ARs alone, but
requires the
presence of a

membrane integrity;
cellular adhesion
Coactivator AR cytoplasmic
trafficking
Direct Hinge
Filamin A NLS? Cross-linking
proteins
Cross-links actin filaments;
recruits F-actin into
extended networks
Corepressor Inhibits N ⁄ C,
suppresses
TIF2 activation
Direct Hinge
Transgelin ()) Cross-linking
proteins
Organizes actin
filaments into dense
meshworks
Corepressor Through ARA 54 Indirect LBD
Actin and ABPs in transcription regulation B. Zheng et al.
2676 FEBS Journal 276 (2009) 2669–2685 ª 2009 The Authors Journal compilation ª 2009 FEBS
SV is localized to the plasma membrane at sites of
intracellular contact. The nuclear localization signal is
located in the middle of this protein [95]. At low den-
sity, SV shows a punctate distribution localized to the
cytoplasm and nucleus, whereas at high density, SV is
localized almost exclusively to the plasma membrane.
SV has been identified as an AR-interacting protein,
which can interact with both N-terminal activation

SV and the minimal functional fragment, also identifies
this potential mechanism. Furthermore, Rac signaling
stimulates membrane ruffling that further attenuates
the coregulator activity of SV. There are two possible
explanations for this: (a) the accumulation of SV in
the membrane prevents it from associating with AR;
and (b) a decrease in the amount of actin monomer
affects SV coregulator activity, which requires actin
monomers [96]. However, SV has no effect on the
cytoplasmic–nuclear translocation of the AR, and does
not affect the half-life of the AR [85].
Gelsolin is a multifunctional ABP, implicated in cell
signaling, cell motility, apoptosis and carcinogenesis
[98,99]. Gelsolin regulates actin polymerization and
depolymerization by sequestering actin monomers, and
can sever and cap actin filaments [1]. Nishimura et al.
[100] identified gelsolin as an AR-interacting protein
that can enhance its transactivation in prostate cancer
cells. Because gelsolin lacks a nuclear localization sig-
nal, it may be cotranslocated into the nucleus upon
binding to other proteins [100]. Like filamin, gelsolin is
able to interact with AR at the time of its nuclear
localization to facilitate the nuclear translocation of
AR [87]. Increased expression of gelsolin can enhance
AR activity under hydroxyflutamide (HF) with low
levels of androgen treatment to maintain AR-mediated
growth and theh survival of tumor cells. Gelsolin itself
interacts with AR LBD via FXXFF and FXXMF
motifs and enhances its activity in the presence of
androgen. The interaction between the N- and C-ter-

ARA54, as well as ARA54 homodimerization, resulting
in enhanced cytoplasmic retention and impaired nuclear
translocation of ARA54 and the AR.
Flightless-1 (Fli-I) is an ABP that can be either asso-
ciated with the cytoskeleton or found in the nucleus,
but its exact physiologic functions have not been eluci-
dated [103]. Fli-I can associate directly with the AR and
function in cooperation with specific combinations of
B. Zheng et al. Actin and ABPs in transcription regulation
FEBS Journal 276 (2009) 2669–2685 ª 2009 The Authors Journal compilation ª 2009 FEBS 2677
other AR coactivators to enhance the ability of the AR
to activate the transcription of AR-regulated genes [77].
Because Fli-I does not enhance AR activity by itself,
but requires the presence of a p160 coactivator, binding
of Fli-I to the AR is apparently insufficient for Fli-I
coactivator function [104]. The contacts between Fli-I
and multiple components in the transcription complex
(AR, glucocorticoid receptor-interacting protein 1,
GRIP1, p160 and coactivator-associated arginine meth-
yltransferase 1, CARM1) may result in more efficient
recruitment of Fli-I to the promoter, a more stable
coactivator complex or a more highly functional con-
formation of the coactivator complex. Fli-I is a second-
ary coactivator in AR transcription activation [104].
a-Actinin-2 is a major structural component of sar-
comeric Z-lines in skeletal muscle, where they function
to anchor actin-containing thin filaments in a constitu-
tive manner [105]. a-Actinin-2 enhances the transacti-
vation activity of SRC-2 and serves as a primary
coactivator for the AR, acting in synergy with SRC-2

in gene expression via either the nuclear shuttling of
transcription factors or the assembly of transcriptional
regulatory complexes [107].
ABPs can recruit multiple components to transcrip-
tion complexes through different types of interactions.
Fli-I binds both actin and the actin-like BAF53 (BAF
complex 53 kDa subunit, BRG1-associated factor), as
well as p160 co-activator [104,108]. Fli-I can help to
secure the association of an SWI ⁄ SNF complex to a
p160 coactivator complex. Fli-I thus helps to coordi-
nate the complementary ATP-dependent nucleosome-
remodeling activity of the SWI ⁄ SNF complex with the
histone acetylating (e.g. from CBP and p300) and
methylating (e.g. from CARM1 and protein arginine
methyltransferase 1) activities of the p160 coactivator
complex [109]. In addition, Fli-I and Fli-I LRR-associ-
ated protein 1 (FLAP1) have an important role in reg-
ulating transcriptional activation by b-catenin and
lymphoid enhancer factor ⁄ T-cell factor (LEF1 ⁄ TCF).
FLAP1 is a key activator, cooperating synergistically
with p300 to enhance LEF1 ⁄ TCF-mediated transcrip-
tion by b-catenin. Fli-I negatively regulates the synergy
of FLAP1 and p300 [103]. Lee & Stallcup [103] found
that Fli-I does not bind well to the p300 KIX domain
and does not appear to inhibit FLAP1–p300 binding,
suggesting that Fli-I does not interfere with the bind-
ing of FLAP1 to p300. Fli-I may exert its negative
influence by inhibiting the activity of FLAP1 and other
essential factors that bind to Fli-I (Fig. 4). It is also
possible that Fli-I may recruit negative regulators, such

(b) Nuclear import of transcriptional regulatory mole-
cules, such as pre-B-cell leukemia transcription factor 1
(PBX1), is regulated by FLNa. Such regulation may
be achieved by the association of FLNa with protein
kinases. That is to say, efficient nuclear localization
of PBX1 and the formation of a transcriptionally
inactive FOXC1–PBX1 complex required FLNa. (c) In
response to cell stimuli and cytoskeletal reorganization,
FLNa expression and the levels of the nuclear FLNa
pool increase. In the nucleus, FLNa acts as a scaffold
for the assembly of FOXC1 and PBX1 transcriptional
inhibitory complexes. Interaction of FOXC1 and
FLNa partitions FOXC1 to HP1a-rich condensed het-
erochromatin in the nucleus and promotes an inhibi-
tory interaction between FOXC1 and PBX1, reducing
FOXC1 transactivity. Furthermore, FOXC1–PBX1
complexes are unable to recruit coactivator complexes
and are targeted to transcriptionally inactive, HP1a-
rich heterochromatin regions of the nucleus [107,110].
That is to say, FLNa can promote the active repres-
sion of FOXC1 activity via an association with inhibi-
tory proteins, rather than simply prevent FOXC1
activation [107]. FLNa also interacts with polyoma
enhancer-binding protein (PEBP2b). FLNa retains
PEBP2b in the cytoplasm, thereby hindering its
engagement as a Runx1 partner. However, PEBP2b is
translocated into the nuclei in cells lacking FLNa,
which enhances the transcriptional activity of
PEBP2 ⁄ CBF. The interaction with FLNa is mediated
by a region within PEBP2b that includes amino acid

with myocardin and enhances myocardin and myocar-
din-related transcription factor (MRTF)-A-dependent
transactivation of smooth muscle a-actin, SM22a and
cardiac atrial natriuretic factor (ANF) promoters in
10T1 ⁄ 2 cells [116]. Hamidouche et al. [117] demon-
strated that FHL2 interacts with b-catenin, a key
player in bone formation induced by Wnt signaling,
which potentiates b-catenin nuclear translocation and
TCF ⁄ LEF transcription, resulting in increased Runx2
and alkaline phosphatase expression.
Human heart LIM protein (hhLIM) participates
in remodeling of the actin cytoskeleton, possibly by
promoting actin bundling [118]. hhLIM has a dual
subcellular location, depending on the context. In the
cytoplasm, hhLIM increases the stability of the actin
cytoskeleton by promoting bundling of actin filaments
[114]. In the nucleus, hhLIM interacts with Nkx2.5
(a cardiac-restricted transcription factor) via its N-ter-
minal LIM domain and enhances the ability of Nkx2.5
to bind to the NKE (Nkx2.5-binding element) boxes in
the ANF promoter. These results suggest that hhLIM
promotes specific expression of the ANF gene by
cooperating with Nkx2.5 [119]. Muscle LIM protein
(MLP) has been found in the nucleus during early
development [120], where it is a potent activator of the
myogenic regulatory factor myoD [121,122]. Lu et al.
[123] showed that MLP promotes specific expression of
the AChR gamma-subunit gene cooperatively with the
myogenin–E12 complex during myogenesis.
B. Zheng et al. Actin and ABPs in transcription regulation

Acknowledgements
This work was supported by the Program for Major
State Basic Research Development Program of China
(No. 2008CB517402), the National Natural Science
Foundation of the People’s Republic of China (No.
30770787, 30670845, 30871272), the New Century
Excellent Talents in University (No. NCET-05-0261),
the Key Project of Chinese Ministry of Education (No.
206016), and the Hebei Natural Science Foundation of
the People’s Republic of China (No. C2008001049).
This research was supported in part by the Intramural
Research Program of the NIH, National Institute on
Aging.
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