The basic helix-loop-helix tal-1 gene plays a key role in hematopoiesis, and its expression is tightly controlled through alternative promoters and complex interactions of cis-acting regulatory elements. tal-1 is not expressed in normal T cells, but its transcription is constitutive in a large proportion of human T cell leukemias. We have previously described a downstream initiation of tal-1 transcription specifically associated with a subset of T cell leukemias that leads to the production of NH 2 -truncated TAL-1 proteins. In this study, we characterize the human promoter (promoter IV), embedded within a GC-rich region in exon IV, responsible for this transcriptional activity. The restriction of promoter IV usage is assured by a novel silencer element in the 3-unstranslated region of the human gene that represses its activity in erythroid but not in T cells. The silencer activity is mediated through binding of a tissue-specific nuclear factor to a novel protein recognition motif (designated tal-RE) in the silencer. Mutation of a single residue within the tal-RE abolishes both specific protein binding and silencing activity. Altogether, our results demonstrate that the tal-1 promoter IV is actively repressed in cells of the erythro-megakaryocytic lineage and that this repression is released in leukemic T cells, resulting in the expression of the tal-1 truncated transcript.
In the rat, the activity of the thermal water of Capvern and of its ionic components on the modification of the flow rate and composition of hepatic bile has been investigated. Two groups of rats were selected: the first group received per os an overload of the thermal water during six weeks. At that time on empty stomach a great increase of biliary phospholipids was observed. An intraduodenal injection of the thermal water produced a significant and rapid increase of biliary flow rate and biliary cholesterol. the animals of the second group received through intraduodenal injections the thermal water or an anionic solution composed of calcium, of magnesium sulphate or of both salts at their concentration in the thermal water, respectively. We observed an increase in biliary flow rate and biliary calcium concentration in the rats receiving the solution of calcium sulphate only and an increase of choleresis in the rats receiving the thermal water only. These data suggest that the thermal water has a specific action on the metabolism of cholesterol in increasing its biliary elimination particularly through the calcium ion content of the water.
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