Interactome Maps of Mouse Gene Regulatory Domains Reveal Basic Principles of Transcriptional Regulation

Authors
Kyong-Rim Kieffer-Kwon,1,12 Zhonghui Tang,2,12 Ewy Mathe,1,12 Jason Qian,1,12 Myong-Hee Sung,3,12 Guoliang Li,2 Wolfgang Resch,1 Songjoon Baek,3 Nathanael Pruett,1 Lars Grøntved,3 Laura Vian,1 Steevenson Nelson,1 Hossein Zare,4 Ofir Hakim,5 Deepak Reyon,6,7 Arito Yamane,1 Hirotaka Nakahashi,1 Alexander L. Kovalchuk,8 Jizhong Zou,9 J. Keith Joung,6,7 Vittorio Sartorelli,4 Chia-Lin Wei,10 Xiaoan Ruan,2 Gordon L. Hager,3,12 Yijun Ruan,2,12
and Rafael Casellas1,11,12,*
01-08-2014
12:00pm
PST
Categories
Transcription Mechanism & Biology
Speaker
Susan Carpenter
Abstract
A key finding of the ENCODE project is that the enhancer landscape of mammalian cells undergoes marked alterations during ontogeny. However, the nature and extent of these changes are unclear. As part of the NIH Mouse Regulome Project, we here combined DNaseI hypersensitivity, ChIP-seq, and ChIA-PET technologies to map the promoterenhancer interactomes of pluripotent ES cells and differentiated B lymphocytes. We confirm that enhancer usage varies widely across tissues. Unexpectedly, we find that this feature extends to broadly transcribed genes, including Myc and Pim1 cell-cycle regulators, which associate with an entirely different set of enhancers in ES and B cells. By means of high-resolution CpG methylomes, genome editing, and digital footprinting, we show that these enhancers recruit lineage-determining factors. Furthermore, we demonstrate that the turning on and off of enhancers during development correlates with promoter activity. We propose that organisms rely on a dynamic enhancer landscape to control basic cellular functions in a tissue-specific manner.