Epigenetic, transcriptional and posttranscriptional regulation of the tyrosine hydroxylase gene

• Published in: International journal of developmental neuroscience 2011-12, Vol.29 (8), p.873-883
• Main Authors: Lenartowski, Robert, Goc, Anna
• Format: Article
• Language: English
• Subjects: Animals; Catecholamines; Chromatin organization; DNA methylation; Epigenesis, Genetic; Gene Expression Regulation, Enzymologic; Humans; Promoter Regions, Genetic; Promoter regulatory elements; RNA Processing, Post-Transcriptional; RNA Stability; RNA, Messenger - genetics; RNA, Messenger - metabolism; TH mRNA stability; Tissue-specific expression; Tyrosine 3-Monooxygenase - genetics; Tyrosine 3-Monooxygenase - metabolism; Tyrosine hydroxylase
• ISSN: 0736-5748; 1873-474X
• DOI: 10.1016/j.ijdevneu.2011.07.006

► Chromatin organization (including nuclear matrix–DNA interactions, DNA methylation and histone modifications) of whole region containing tyrosine hydroxylase gene is involved in its regulation. ► Cis-acting elements mediating developmental, tissue- and cell-specific transcription of the TH gene are found in promoter, coding sequence, first intron and 3′ UTR. ► Not only transcription initiation but also its elongation are regulated in case of TH gene. ► Posttranscriptional mechanisms of the TH gene regulation involve alternative splicing, differential mRNA stability and translatability. The activity of tyrosine hydroxylase (TH, EC 1.14.16.2) gene and protein determines the catecholamine level, which, in turn, is crucial for the organism homeostasis. The TH gene expression is regulated by near all possible regulatory mechanisms on epigenetic, transcriptional and posttranscriptional levels. Ongoing molecular characteristic of the TH gene reveals some of the cis and trans elements necessary for its proper expression but most of them especially these responsible for tissue specific expression remain still obscure. This review will focus on some aspects of TH regulation including spatial chromatin organization of the TH locus and TH gene, regulatory elements mediating basal, induced and cell-specific activity, transcriptional elongation, alternative TH RNA processing, and the regulation of TH RNA stability in the cell.