Conserved and unique sequences in the 3′-untranslated region of rat smooth-muscle alpha-actin mRNA

Hsu, Chin-Yi Jenny; Frankel, Fred R.

doi:10.1016/0378-1119(88)90445-3

“…Finally, a third mechanism whereby TGF-␤ could increase SM ␣-actin expression in non-SMCs is through some posttranscriptional control mechanisms, including stabilization of SM ␣-actin mRNA. 22,32,33 Whether these mechanisms contribute to TGF-␤ induction of SM ␣-actin in fibroblasts and ECs requires further investigation.…”

Section: Discussionmentioning

confidence: 99%

Similarities and Differences in Smooth Muscle α-Actin Induction by TGF-β in Smooth Muscle Versus Non–Smooth Muscle Cells

Hautmann

¹

,

Adam

²

,

Owens

³

1999

ATVB

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Abstract-Transforming growth factor-␤ (TGF-␤) has been shown to stimulate smooth muscle (SM) ␣-actin expression in smooth muscle cells (SMCs) and non-SMCs. We previously demonstrated that the 2 CArG boxes A and B and a novel TGF-␤ control element (TCE) located within the first 125 bp of the SM ␣-actin promoter were required for TGF-␤ inducibility of SM ␣-actin in SMCs. The aims of the present study were (1) to determine whether the TCE exhibits SMC specificity or contributes to TGF-␤ induction of SM ␣-actin expression in non-SMCs (ie, endothelial cells and fibroblasts) and (2) to determine whether TGF-␤ can induce expression of multiple TCE-containing SMC differentiation marker genes, such as SM22␣, h 1 calponin, and SM myosin heavy chain (SM MHC) in non-SMCs. Results of transient transfection assays demonstrated that mutation of CArG A, CArG B, or the TCE within a 125-bp promoter context completely abolished TGF-␤ inducibility of SM ␣-actin in endothelial cells and fibroblasts. However, in contrast to observations in SMCs, inclusion of regions upstream from Ϫ155 completely repressed TGF-␤ responsiveness in non-SMCs. Electrophoretic mobility shift assays showed that TGF-␤ enhanced binding of a serum response factor to the CArG elements and the binding of an as-yet-unidentified factor to the TCE in endothelial cells and fibroblasts, but to a much lesser extent compared with SMCs. TGF-␤ also stimulated expression of the SMC differentiation marker SM22␣ in non-SMCs. However, in contrast to SMCs, TGF-␤ did not induce expression of h 1 calponin and SM MHC in non-SMCs. In summary, these results suggest a conserved role for CArG A, CArG B, and the TCE in TGF-␤-induced expression of SM ␣-actin in SMCs and non-SMCs that is modified by a complex interplay of positive-and negative-acting cis elements in a cell-specific manner. Furthermore, observations that TGF-␤ stimulated expression of several early but not late differentiation markers in non-SMCs indicate that TGF-␤ alone is not sufficient to induce transdifferentiation of non-SMCs into SMCs.

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“…In fact, nucleotide sequence analysis of a human ZFX cDNA reveals that its 3' UTR is 83% identical to 2.7 kb of the mouse Zfx 3' UTR (Schneider-Gadicke et al, in press). Conservation of long segments of 3' UTRs has been observed in several other genes (14,18,20,21,34 (Fig. 2A, probe 2) was hybridized at low stringency to EcoRI-digested male (XY) and female (XX) genomic DNAs from a variety of mammals.…”

Section: S I H T K D Y P H R C E Y C K K G F R R P S E K N Q H I M mentioning

confidence: 85%

Mouse Zfx protein is similar to Zfy-2: each contains an acidic activating domain and 13 zinc fingers.

Mardon

¹

,

Luoh

²

,

Simpson

³

et al. 1990

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The Zfy gene is located on the Y chromosome of placental mammals and encodes a zinc finger protein which may serve as the primary sex-determining signal. A related gene, Zfx, is similarly conserved on the X chromosome. Unlike that in most mammals, the mouse genome contains four homologous zinc finger loci: Zfy-1, Zfy-2, Zfx, and Zfa (on an autosome). We report that, in contrast to the mouse Zfy genes, Zfx is widely transcribed in embryos, newborns, and adults, both male and female. Moreover, Zfx transcripts contain long 3' untranslated sequences which are phylogenetically conserved. Zfa is a processed gene derived from Zfx. An analysis of cDNA clones demonstrated that Zfx encodes a 799-amino-acid protein that is 70% identical to the mouse Zfy-1 and Zfy-2 proteins. Zfx, Zfy-1, and Zfy-2 contain highly acidic amino-terminal domains and carboxy-terminal regions containing 13 zinc fingers. When fused to the DNA-binding domain of GAL4, the acidic domains of Zfx and Zfy-2 activated transcription in yeast cells.

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Mouse Zfx Protein Is Similar to Zfy-2: Each Contains an Acidic Activating Domain and 13 Zinc Fingers

Mardon

¹

,

Luoh

²

,

Simpson

³

et al. 1990

Molecular and Cellular Biology

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The Zfy gene is located on the Y chromosome of placental mammals and encodes a zinc finger protein which may serve as the primary sex-determining signal. A related gene, Zfx, is similarly conserved on the X chromosome. Unlike that in most mammals, the mouse genome contains four homologous zinc finger loci: Zfy-1, Zfy-2, Zfx, and Zfa (on an autosome). We report that, in contrast to the mouse Zfy genes, Zfx is widely transcribed in embryos, newborns, and adults, both male and female. Moreover, Zfx transcripts contain long 3' untranslated sequences which are phylogenetically conserved. Zfa is a processed gene derived from Zfx. An analysis of cDNA clones demonstrated that Zfx encodes a 799-amino-acid protein that is 70% identical to the mouse Zfy-1 and Zfy-2 proteins. Zfx, Zfy-1, and Zfy-2 contain highly acidic amino-terminal domains and carboxy-terminal regions containing 13 zinc fingers. When fused to the DNA-binding domain of GAL4, the acidic domains of Zfx and Zfy-2 activated transcription in yeast cells.

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Conserved and unique sequences in the 3′-untranslated region of rat smooth-muscle alpha-actin mRNA

Cited by 3 publications

References 12 publications

Similarities and Differences in Smooth Muscle α-Actin Induction by TGF-β in Smooth Muscle Versus Non–Smooth Muscle Cells

Similarities and Differences in Smooth Muscle α-Actin Induction by TGF-β in Smooth Muscle Versus Non–Smooth Muscle Cells

Mouse Zfx protein is similar to Zfy-2: each contains an acidic activating domain and 13 zinc fingers.

Mouse Zfx Protein Is Similar to Zfy-2: Each Contains an Acidic Activating Domain and 13 Zinc Fingers

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