共查询到20条相似文献,搜索用时 46 毫秒
1.
2.
Serum response factor micromanaging cardiogenesis 总被引:3,自引:0,他引:3
3.
4.
5.
6.
Barron MR Belaguli NS Zhang SX Trinh M Iyer D Merlo X Lough JW Parmacek MS Bruneau BG Schwartz RJ 《The Journal of biological chemistry》2005,280(12):11816-11828
We tested the idea that T-box factors direct serum response factor (SRF) gene activity early in development. Analysis of SRF-LacZ "knock-in" mice showed highly restricted expression in early embryonic cardiac and skeletal muscle mesoderm and neuroectoderm. Examination of the SRF gene for regulatory regions by linking the promoter and 5'-flanking sequences, up to 5.5 kb, failed to target LacZ transgene activity to the heart and the tail pre-somitic mesenchyme. However, linkage of a minimal SRF promoter with the SRF 3'-untranslated region (UTR), inundated with multimeric T-box binding sites (TBEs), restored robust reporter gene activity to embryonic heart and tail. Finer dissection of the 3'-UTR to a small cluster of TBEs also stimulated transgene activity in the cardiac forming region and the tail, however, when the TBEs contained within these DNA sequences were mutated, preventing Tbx binding, transgene activity was lost. Tbx2, Tbx5, and the cardiac-enriched MYST family histone acetyltransferase TIP60, were observed to be mutual interactive cofactors through the TIP60 zinc finger and the T-box of the Tbx factors. In SRF-null ES cells, TIP60, Tbx2, and Tbx5 were sufficient to stimulate co-transfected SRF reporter activity, however this activity required the presence of the SRF 3'-UTR. SRF gene transactivation was blocked by two distinct TIP60 mutants, in which either the histone acetyltransferase domain was inactivated or the Zn finger-protein binding domain was excised. Our study supports the idea that SRF embryonic cardiac gene expression is dependent upon the SRF 3'-UTR enhancer, Tbx2, Tbx5, and TIP60 histone acetyltransferase activity. 相似文献
7.
8.
9.
10.
Activation of cardiac gene expression by myocardin, a transcriptional cofactor for serum response factor. 总被引:40,自引:0,他引:40
D Wang P S Chang Z Wang L Sutherland J A Richardson E Small P A Krieg E N Olson 《Cell》2001,105(7):851-862
11.
12.
13.
14.
15.
16.
Mirza M Marston S Willott R Ashley C Mogensen J McKenna W Robinson P Redwood C Watkins H 《The Journal of biological chemistry》2005,280(31):28498-28506
Dilated cardiomyopathy (DCM), characterized by cardiac dilatation and contractile dysfunction, is a major cause of heart failure. Inherited DCM can result from mutations in the genes encoding cardiac troponin T, troponin C, and alpha-tropomyosin; different mutations in the same genes cause hypertrophic cardiomyopathy. To understand how certain mutations lead specifically to DCM, we have investigated their effect on contractile function by comparing wild-type and mutant recombinant proteins. Because initial studies on two troponin T mutations have generated conflicting findings, we analyzed all eight published DCM mutations in troponin T, troponin C, and alpha-tropomyosin in a range of in vitro assays. Thin filaments, reconstituted with a 1:1 ratio of mutant/wild-type proteins (the likely in vivo ratio), all showed reduced Ca(2+) sensitivity of activation in ATPase and motility assays, and except for one alpha-tropomyosin mutant showed lower maximum Ca(2+) activation. Incorporation of either of two troponin T mutants in skinned cardiac trabeculae also decreased Ca(2+) sensitivity of force generation. Structure/function considerations imply that the diverse thin filament DCM mutations affect different aspects of regulatory function yet change contractility in a consistent manner. The DCM mutations depress myofibrillar function, an effect fundamentally opposite to that of hypertrophic cardiomyopathy-causing thin filament mutations, suggesting that decreased contractility may trigger pathways that ultimately lead to the clinical phenotype. 相似文献
17.
Dominant Negative Murine Serum Response Factor: Alternative Splicing within the Activation Domain Inhibits Transactivation of Serum Response Factor Binding Targets
下载免费PDF全文
![点击此处可从《Molecular and cellular biology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Narasimhaswamy S. Belaguli Wei Zhou Thuy-Hanh T. Trinh Mark W. Majesky Robert J. Schwartz 《Molecular and cellular biology》1999,19(7):4582-4591
18.
Cardiomyopathy in transgenic mice with cardiac-specific overexpression of serum response factor 总被引:1,自引:0,他引:1
Zhang X Azhar G Chai J Sheridan P Nagano K Brown T Yang J Khrapko K Borras AM Lawitts J Misra RP Wei JY 《American journal of physiology. Heart and circulatory physiology》2001,280(4):H1782-H1792
19.