Interactome maps of mouse gene regulatory domains reveal basic principles of transcriptional regulation.
Document Type
Article
Publication Date
12-19-2013
JAX Source
Cell 2013 Dec 19; 155(7):1507-20.
Volume
155
Issue
7
First Page
1507
Last Page
1520
ISSN
1097-4172
PMID
24360274
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.
Cell 2013 Dec 19; 155(7):1507-20.
Recommended Citation
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 A,
Zou J,
Joung J,
Sartorelli V,
Wei C,
Ruan X,
Hager G,
Ruan Y,
Casellas R.
Interactome maps of mouse gene regulatory domains reveal basic principles of transcriptional regulation. Cell 2013 Dec 19; 155(7):1507-20.