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.During early development, a subset of pluripotent mesodermal cells becomes increasingly committed to the cardiac muscle lineage, through the combinatorial interactions of transcription factors, which result in the expression of cardiac-specific genes. Although this is a continuous developmental process, one transcription factor, serum response factor (SRF), 1 may play a leading role in the commitment of pre-cardiac cells. SRF is a 67-kDa DNA-binding protein that was first cloned from a HeLa cDNA library and was generally presumed to be a ubiquitous transcription factor (1). SRF binds DNA as a dimer and symmetrically contacts various serum response elements with a consensus sequence CC(A/T) 6 GG. SRF is member of the "MADS" box transcription factor family (2, 3), and, despite their similarities, MADS box proteins have evolved to perform disparate important biological functions. Functions of MADS transcription factors include specification of mating type in yeast, homeotic activities in plants, pharyngeal muscle specification in Caenorhabditis elegans, pulmonary development in Drosophila, and elaboration of mesoderm structures in vertebrates (reviewed in Ref. 4). Recent homologous recombinant knock-out of the murine SRF gene locus supports the observation that SRF is absolutely required for the appearance of mesoderm during mouse gastrulation (5).Analysis of SRF null mice not only reve...
A series of room temperature ionic liquids bearing hydroxyl groups, namely 1-(3’-hydroxyl-n-propyl)-3-alkylimidazolium tetrafluoroborate or hexafluorophosphate, were prepared and characterized. Their typical physical properties were also determined. The tribological test results show that these ionic liquids possess better friction-reducing and anti-wear ability for aluminum-on-steel system than lubricant X-1P. The friction coefficients of them are little higher than that of the nonfunctionlized ionic liquid LP308, while they possess better anti-wear abilities than the latter, which may ascribe to the chemical activity of hydroxyl group. Both the anions and the side substituted alkyl chains attached to the imidazolium cations affect the tribological performance of the lubricants. The SEM, EDS and XPS analysis of the worn surfaces show that complicated tribo-chemical reactions were involved in the sliding process. The boundary films composed of fluorides, nitrogen oxide, BN, and FePO4 were generated on the rubbing aluminum surfaces, which contribute to effectively decreasing the friction and wear of the contacts.
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