Author/Authors :
Kyong-Rim Kieffer-Kwon، نويسنده , , Zhonghui Tang، نويسنده , , Ewy Mathe، نويسنده , , Jason Qian، نويسنده , , Myong-Hee Sung، نويسنده , , Guoliang Li، نويسنده , , Wolfgang Resch، نويسنده , , Songjoon Baek، نويسنده , , Nathanael Pruett، نويسنده , , Lars Gr?ntved، نويسنده , , Laura Vian، نويسنده , , Steevenson Nelson، نويسنده , , Hossein Zare، نويسنده , , Ofir Hakim، نويسنده , , Deepak Reyon، نويسنده , , Arito Yamane، نويسنده , , Hirotaka Nakahashi، نويسنده , , Alexander L. Kovalchuk، نويسنده , , Jizhong Zou، نويسنده , , J. Keith Joung، نويسنده , , et al.، نويسنده ,
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 promoter-enhancer 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.
