Bile acids and gene regulation: from nuclear receptors to chromatin.
Transcription regulation by bile acids is far more complicated than it appeared at first when several groups began their investigations in the early '90. It has become clear now that bile acids regulate the transcription of genes involved in bile acid synthesis, transport and other metabolic pathways via multiple mechanisms that involve transcription factors, nuclear receptors, coregulators, chromatin and the related modifying enzyme complexes. At a first look this might seem surprising but if one considers the physical-chemical properties of these molecules it should be evident that, due to their detergent properties, bile acids may be harmful if they reach high concentrations in the liver and intestine. Therefore, living organisms have developed biochemical mechanisms that finely tune the concentration of bile acids according to the body needs and in response to environmental challenges. In this review, we will discuss the most recent evidences on the mechanisms through which bile acids regulate gene transcription, including the function of nuclear receptors and emphasizing the emerging role of chromatin and the associated modifying enzymes.
Department of Pharmacological Sciences, University of Milan, via Balzaretti 9, 20133 Milan, Italy.
Nico
N
Mitro
Federica
F
Gilardi
Cristina
C
Godio
Elena
E
Scotti
Emma
E
De Fabiani
Donatella
D
Caruso
Maurizio
M
Crestani
D000818:Animals; D001647:Bile Acids and Salts / Q000494:pharmacology*; D002790:Cholesterol 7-alpha-Hydroxylase / Q000187:drug effects / Q000235:genetics; D002843:Chromatin / Q000187:drug effects / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D051379:Mice; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D014157:Transcription Factors / Q000187:drug effects / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects; D000099150:Receptor, Farnesoid X-Activated
D001647:Bile Acids and Salts; D002790:Cholesterol 7-alpha-Hydroxylase; D002843:Chromatin; D004268:DNA-Binding Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D000099150:Receptor, Farnesoid X-Activated; C502772:Cyp7a1 protein, mouse