scholarly journals Target Gene-Specific Modulation of Myocardin Activity by GATA Transcription Factors

2004 ◽  
Vol 24 (19) ◽  
pp. 8519-8528 ◽  
Author(s):  
Jiyeon Oh ◽  
Zhigao Wang ◽  
Da-Zhi Wang ◽  
Ching-Ling Lien ◽  
Weibing Xing ◽  
...  

ABSTRACT Myocardin is a transcriptional coactivator that regulates cardiac and smooth muscle gene expression by associating with serum response factor. We show that GATA transcription factors can either stimulate or suppress the transcriptional activity of myocardin, depending on the target gene. Modulation of myocardin activity by GATA4 is mediated by the physical interaction of myocardin with the DNA binding domain of GATA4 but does not require binding of GATA4 to DNA. Paradoxically, the transcription activation domain of GATA4 is dispensable for the stimulatory effect of GATA4 on myocardin activity but is required for repression of myocardin activity. The ability of GATA transcription factors to modulate myocardin activity provides a potential mechanism for fine tuning the expression of serum response factor target genes in a gene-specific manner.

2002 ◽  
Vol 22 (20) ◽  
pp. 7083-7092 ◽  
Author(s):  
Kasumi Murai ◽  
Richard Treisman

ABSTRACT Serum response factor (SRF) is a transcription factor which regulates many immediate-early genes. Rho GTPases regulate SRF activity through changes in actin dynamics, but some SRF target genes, such as c-fos, are insensitive to this pathway. At the c-fos promoter, SRF recruits members of the ternary complex factor (TCF) family of Ets domain proteins through interactions with the TCF B-box region. Analysis of c-fos promoter mutations demonstrates that the TCF and ATF/AP1 sites adjoining the SRF binding site inhibit activation of the promoter by RhoA-actin signaling. The presence of the TCF binding site is sufficient for inhibition, and experiments with an altered-specificity Elk-1 derivative demonstrate that inhibition can be mediated by the Elk-1 TCF. Using Elk-1 fusion proteins that can bind DNA autonomously, we show that inhibition of RhoA-actin signaling requires physical interaction between the Elk-1 B box and SRF. These results account for the insensitivity of c-fos to RhoA-actin signaling. Interaction of the B box with SRF also potentiates transcriptional activation by the Elk-1 C-terminal activation domain. Combinatorial interactions between SRF and TCF proteins are thus likely to play an important role in determining the relative sensitivity of SRF target genes to Ras- and Rho-controlled signal transduction pathways.


2004 ◽  
Vol 280 (6) ◽  
pp. 4125-4134 ◽  
Author(s):  
Jeffrey W. Streb ◽  
Joseph M. Miano

2019 ◽  
Vol 33 (S1) ◽  
Author(s):  
Gopalkrishna Sreejit ◽  
Nosirudeen Quadri ◽  
Radha Ananthakrishnan ◽  
Ann Marie Schmidt ◽  
Ravichandran Ramasamy

1994 ◽  
Vol 14 (5) ◽  
pp. 3283-3291 ◽  
Author(s):  
P Shore ◽  
A D Sharrocks

Transcriptional induction of the c-fos gene in response to epidermal growth factor stimulation is mediated in part by a ternary nucleoprotein complex within the promoter consisting of serum response factor (SRF), p62TCF/Elk-1 and the serum response element (SRE). Both SRF and p62TCF/Elk-1 contact the DNA and bind in a cooperative manner to the SRE. In this study, we demonstrate that SRF and Elk-1 interact directly in the absence of the SRE. A 30-amino-acid peptide from Elk-1 (B-box) is both necessary and sufficient to mediate protein-protein contacts with SRF. Moreover, the Elk-1 B-box is necessary to enable SRF-dependent binding of an alternative ETS domain (from the transcription factor PU.1) to the c-fos SRE. Mutations in either the Elk-1 B-box or the C-terminal half of the SRF DNA-binding domain (coreSRF) which show reduced ability to form ternary complexes also show greatly reduced protein-protein interactions in the absence of the SRE. Our results clearly demonstrate that direct protein-protein interactions between the transcription factors Elk-1 and SRF, in addition to DNA contacts, contribute to the formation of a ternary complex on the c-fos SRE. We discuss the wider applicability of our results in describing specific protein-protein interactions between short well-defined transcription factor domains.


1996 ◽  
Vol 271 (9) ◽  
pp. 5258-5264 ◽  
Author(s):  
Regina Groisman ◽  
Hiroshi Masutani ◽  
Marie-Pierre Leibovitch ◽  
Philippe Robin ◽  
Isabelle Soudant ◽  
...  

1998 ◽  
Vol 273 (17) ◽  
pp. 10506-10514 ◽  
Author(s):  
Yan Ling ◽  
Adam G. West ◽  
E. Claire Roberts ◽  
Jeremy H. Lakey ◽  
Andrew D. Sharrocks

1995 ◽  
Vol 15 (7) ◽  
pp. 3672-3684 ◽  
Author(s):  
C K Miranti ◽  
D D Ginty ◽  
G Huang ◽  
T Chatila ◽  
M E Greenberg

Enhanced levels of cytoplasmic Ca2+ due to membrane depolarization with elevated levels of KCl or exposure to the Ca2+ ionophore ionomycin stimulate serum response element (SRE)-dependent transcription in the pheochromocytoma cell line PC12. By using altered binding specificity mutants of transcription factors that bind to the SRE, it was demonstrated that in contrast to treatment with purified growth factors, such as nerve growth factor, the serum response factor (SRF), but not Elk-1, mediates Ca(2+)-regulated SRE-dependent transcription. Enhanced levels of cytoplasmic Ca2+ were found to trigger SRE-dependent transcription via a Ras-independent signaling pathway that appears to involve a Ca2+/calmodulin-dependent kinase (CaMK). Overexpression of a constitutively active form of CaMKIV stimulated SRF-dependent transcription. Taken together, these findings indicate that SRF is a versatile transcription factor that, when bound to the SRE, can function by distinct mechanisms and can mediate transcriptional responses to both CaMK- and Ras-dependent signaling pathways.


2008 ◽  
Vol 316 (2) ◽  
pp. 260-274 ◽  
Author(s):  
María Galardi-Castilla ◽  
Barbara Pergolizzi ◽  
Gareth Bloomfield ◽  
Jason Skelton ◽  
Al Ivens ◽  
...  

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