Mechanisms of IL-10 gene regulation in immune cells:
Role of cis-regulatory elements
Post full genome sequencing of the mice and human genome, the presence of Conserved Non-coding Sequences (CNS) between different species was identified for multiple genes. Of them, we are interested in CNS-9, which is located 9kb upstream of the IL-10 transcription start site. CNS-9 is a key cis-acting element of IL-10 regulation in various immune cells. To determine the molecular mechanism, we are checking for gene looping between CNS-9 and other cis-regulatory elements, and are identifying proteins or regulatory DNA elements that bind to CNS-9. To elucidate the functional importance of CNS-9 for IL-10, we have generated CNS-9 deficient mice. We will utilize these mice to check the importance of CNS-9 for IL-10 expression in diverse immune cells in homeostatic and disease situations.