**Acknowledgements**

*Gene Expression and Control*

**90**

**Figure 5.**

factors that regulate expression of urea cycle genes could provide a clue about amino acid(s) and metabolites that act as sensors of the dietary protein intake. Data mining of the ENCODE and Cistrome databases presented here revealed that transcription factor RXRA binds to regulatory elements of *NAGS*, *CPS1*, and *OTC* genes. The RXRA transcription factor regulates gene expression by forming heterodimers with several transcription factors including peroxisome proliferatoractivated receptor gamma (PPARγ), which regulated glucose metabolism [80]. If future studies show that PPARγ-RXRA heterodimer regulates expression of the *NAGS*, *CPS1*, and *OTC* genes, that would suggest that glucose, rather than amino acid(s), might be a sensor of the balance of protein and carbohydrate intake that regulates expression of the urea cycle genes. Although similar data sets are not yet available for the human small intestine cells, the ENCODE project is ongoing and future data mining efforts will provide a more complete information about transcriptional regulation of the *NAGS*, *CPS1*, and *OTC* genes. Similarly, the Cistrome

*Overview of the OTC genomic region. (A) Binding sites for chromatin remodeling proteins. (B) Epigenetic marks. (C) Transcription factor binding sites. (D) Map and sequence conservation of the OTC genomic region.*

This work was supported by public health service grants K01DK076846 and R01DK064913 from the National Institute of Diabetes Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services.
