Advances in Transcriptional Control

*Gene Expression and Control*

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for adaptations to these dietary changes.

**Chapter 5**

Genes

**Abstract**

**1. Introduction**

*Ljubica Caldovic*

Data Mining Approaches for

Understanding of Regulation

of Expression of the Urea Cycle

Urea cycle converts ammonia, a waste product of protein catabolism and a neurotoxin, into non-toxic urea. Urea cycle disorders are a group of rare genetic diseases that have protein-restricted diet as a common treatment modality. Expression of urea cycle genes is regulated in concert by the dietary protein intake, but the mechanism of this regulation is not well understood. Data mining of databases such as ENCODE and Cistrome can be used to gain new information about regulatory elements, transcription factors, and epigenetic mechanisms that regulate expression of urea cycle genes. This can lead to better understanding of the common mechanism, which regulates urea cycle genes, and can generate testable hypotheses about regulation of gene expression and new treatments for urea cycle disorders.

**Keywords:** urea cycle, transcriptional regulation, transcription factor, data mining,

Transcriptional regulation of gene expression is essential for development, tissue differentiation, and organisms' responses to changes in their environment. Maintenance of homeostasis would be impossible without regulation of expression of genes that code for enzymes in the carbohydrate, fat, and protein metabolism. Omnivorous mammals, such as humans, mice, and rats, can adapt their metabolism to varying proportions of amino acids, fats, and carbohydrates as sources of energy [1, 2]. Strict carnivores, such as cats, lack such adaptive mechanisms [3]. Diet rich in carbohydrates and fats triggers utilization of these nutrients as sources of energy and storage of excess sugars and fat in the form of glycogen and adipose tissue [1, 4]. On the other hand, a diet rich in proteins imposes changes in nitrogen balance because excess proteins and amino acids cannot be stored [1]. High intake of proteins, combined with low intake of carbohydrates and fats, leads to utilization of amino acids as energy sources and results in increased catabolism of amino acids [1, 4] and increased need to dispose of waste nitrogen, generated in this process. Transcriptional regulation of expression of enzymes in the pathways for degradation of nutrients as well as biosynthesis of molecules that can be stored is necessary

ChIP-Seq, epigenetic, histone modification, chromatin remodeler
