UTF1 is a chromatin-associated protein involved in ES cell differentiation

Embryonic stem (ES) cells are able to grow indefinitely (self-renewal) and have the potential to differentiate into all adult cell types (pluripotency). The regulatory network that controls pluripotency is well characterized, whereas the molecular basis for the transition from self-renewal to the differentiation of ES cells is much less understood, although dynamic epigenetic gene silencing and chromatin compaction are clearly implicated. In this study, we report that UTF1 (undifferentiated embryonic cell transcription factor 1) is involved in ES cell differentiation. Knockdown of UTF1 in ES and carcinoma cells resulted in a substantial delay or block in differentiation. Further analysis using fluorescence recovery after photobleaching assays, subnuclear fractionations, and reporter assays revealed that UTF1 is a stably chromatin-associated transcriptional repressor protein with a dynamic behavior similar to core histones. An N-terminal Myb/SANT domain and a C-terminal domain containing a putative leucine zipper are required for these properties of UTF1. These data demonstrate that UTF1 is a strongly chromatin-associated protein involved in the initiation of ES cell differentiation

Hepatic Farnesoid X-Receptor Isoforms α2 and α4 Differentially Modulate Bile Salt and Lipoprotein Metabolism in Mice

The nuclear receptor FXR acts as an intracellular bile salt sensor that regulates synthesis and transport of bile salts within their enterohepatic circulation. In addition, FXR is involved in control of a variety of crucial metabolic pathways. Four FXR splice variants are known, i.e. FXRα1-4. Although these isoforms show differences in spatial and temporal expression patterns as well as in transcriptional activity, the physiological relevance hereof has remained elusive. We have evaluated specific roles of hepatic FXRα2 and FXRα4 by stably expressing these isoforms using liver-specific self-complementary adeno-associated viral vectors in total body FXR knock-out mice. The hepatic gene expression profile of the FXR knock-out mice was largely normalized by both isoforms. Yet, differential effects were also apparent; FXRα2 was more effective in reducing elevated HDL levels and transrepressed hepatic expression of Cyp8b1, the regulator of cholate synthesis. The latter coincided with a switch in hydrophobicity of the bile salt pool. Furthermore, FXRα2-transduction caused an increased neutral sterol excretion compared to FXRα4 without affecting intestinal cholesterol absorption. Our data show, for the first time, that hepatic FXRα2 and FXRα4 differentially modulate bile salt and lipoprotein metabolism in mice

Metabolic Effects of Bile Acids in the Gut in Health and Disease

In the last decade, it became clear that bile acids, in addition to their role in intestinal absorption of lipids and fat-soluble vitamins, are major regulators of metabolism. They activate signal transduction pathways through binding to the specific bile acid receptors TGR5 and FXR. Indirectly, bile acids influence metabolism via modification of the gut microbiota ecosystem. The relation between bile acid metabolism and gut microbiota composition is very complex whereas gut microbiota modulates bile acid structure, creating a complex bile acid pool consisting of a mixture of differentially structured species, bile acids alter gut microbiota by disturbing bacterial membrane integrity. In addition, to the effects on glucose and energy homeostasis, recent literature ascribed a role for bile acid signaling in control of inflammation and regulation of the nervous system. In this review, we discuss a selection of recent published studies describing the effects of intestinal bile acid signaling on health and disease

Metabolic Effects of Bile Acids in the Gut in Health and Disease

In the last decade, it became clear that bile acids, in addition to their role in intestinal absorption of lipids and fat-soluble vitamins, are major regulators of metabolism. They activate signal transduction pathways through binding to the specific bile acid receptors TGR5 and FXR. Indirectly, bile acids influence metabolism via modification of the gut microbiota ecosystem. The relation between bile acid metabolism and gut microbiota composition is very complex whereas gut microbiota modulates bile acid structure, creating a complex bile acid pool consisting of a mixture of differentially structured species, bile acids alter gut microbiota by disturbing bacterial membrane integrity. In addition, to the effects on glucose and energy homeostasis, recent literature ascribed a role for bile acid signaling in control of inflammation and regulation of the nervous system. In this review, we discuss a selection of recent published studies describing the effects of intestinal bile acid signaling on health and disease

Metabolic Effects of Bile Acids in the Gut in Health and Disease

In the last decade, it became clear that bile acids, in addition to their role in intestinal absorption of lipids and fat-soluble vitamins, are major regulators of metabolism. They activate signal transduction pathways through binding to the specific bile acid receptors TGR5 and FXR. Indirectly, bile acids influence metabolism via modification of the gut microbiota ecosystem. The relation between bile acid metabolism and gut microbiota composition is very complex whereas gut microbiota modulates bile acid structure, creating a complex bile acid pool consisting of a mixture of differentially structured species, bile acids alter gut microbiota by disturbing bacterial membrane integrity. In addition, to the effects on glucose and energy homeostasis, recent literature ascribed a role for bile acid signaling in control of inflammation and regulation of the nervous system. In this review, we discuss a selection of recent published studies describing the effects of intestinal bile acid signaling on health and disease