Digging deeper into the basic principles of gene regulation

2013

Challenge

Transcription, the first step in determining which genes are expressed, is largely controlled by regulatory pieces of DNA. The global mapping of cellular regulatory elements—termed the ‘regulome’—has become possible thanks to advances in sequencing technologies, leading to important discoveries of how critical genes are regulated. However, researchers are still trying to chart how different regulatory elements interact, a critical piece in understanding gene transcription.

Advance

IRP researchers led by Rafael Casellas, Ph.D., generated maps depicting regulatory element interactions in both pluripotent embryonic stem (ES) cells and differentiated B lymphocytes. Unexpectedly, they found that genes with similar levels of expression in both cell types are often controlled by different regulatory elements, a finding that hints at the importance of tissue specificity in controlling gene expression.

Impact

The new interaction maps provide a rich resource for the scientific community, enabling the assessment of transcription regulation on a genome scale and allowing researchers to better study genes of therapeutic interest.

Publications

Kieffer Kwon K, Tang Z, Mathe E, Qian J, Sung M, Li G, Resch W, Baek S, Pruett N, Grøntved L, Vian L, Nelson S, Zare H, Hakim O, Reyon D, Yamane A, Nakahashi H, Kovalchuk AL, Zou J, Joung JK, Sartorelli V, Wei CL, Ruan X, Hager GL, Ruan Y, Casellas R. (2013). Interactome maps of mouse gene regulatory domains reveal basic principles of transcriptional regulation. Cell. 155(7), 1507-20.