Static and Dynamic DNA Loops form AP-1-Bound Activation Hubs during Macrophage Development.

TitleStatic and Dynamic DNA Loops form AP-1-Bound Activation Hubs during Macrophage Development.
Publication TypeJournal Article
Year of Publication2017
AuthorsPhanstiel, Douglas H., Kevin Van Bortle, Damek Spacek, Gaelen T. Hess, Muhammad Saad Shamim, Ido Machol, Michael I. Love, Erez Lieberman Aiden, Michael C. Bassik, and Michael P. Snyder
JournalMol Cell
Volume67
Issue6
Pagination1037-1048.e6
Date Published2017 Sep 21
ISSN1097-4164
KeywordsBinding Sites, Cell Differentiation, Cell Line, Tumor, Chromatin, Chromatin Assembly and Disassembly, DNA, Enhancer Elements, Genetic, Gene Expression Regulation, High-Throughput Nucleotide Sequencing, Humans, Macrophages, Nucleic Acid Conformation, Phenotype, Protein Binding, Time Factors, Transcription Factor AP-1, Transcription, Genetic
Abstract

The three-dimensional arrangement of the human genome comprises a complex network of structural and regulatory chromatin loops important for coordinating changes in transcription during human development. To better understand the mechanisms underlying context-specific 3D chromatin structure and transcription during cellular differentiation, we generated comprehensive in situ Hi-C maps of DNA loops in human monocytes and differentiated macrophages. We demonstrate that dynamic looping events are regulatory rather than structural in nature and uncover widespread coordination of dynamic enhancer activity at preformed and acquired DNA loops. Enhancer-bound loop formation and enhancer activation of preformed loops together form multi-loop activation hubs at key macrophage genes. Activation hubs connect 3.4 enhancers per promoter and exhibit a strong enrichment for activator protein 1 (AP-1)-binding events, suggesting that multi-loop activation hubs involving cell-type-specific transcription factors represent an important class of regulatory chromatin structures for the spatiotemporal control of transcription.

DOI10.1016/j.molcel.2017.08.006
Alternate JournalMol Cell
Original PublicationStatic and dynamic DNA loops form AP-1-bound activation hubs during macrophage development.
PubMed ID28890333
PubMed Central IDPMC5610110
Grant ListU01 HL130010 / HL / NHLBI NIH HHS / United States
UM1 HG009375 / HG / NHGRI NIH HHS / United States
K99 HG008662 / HG / NHGRI NIH HHS / United States
R00 HG008662 / HG / NHGRI NIH HHS / United States
F32 DK107112 / DK / NIDDK NIH HHS / United States
DP2 OD008540 / OD / NIH HHS / United States
P50 HG006193 / HG / NHGRI NIH HHS / United States
T32 HG000044 / HG / NHGRI NIH HHS / United States
P01 CA142538 / CA / NCI NIH HHS / United States
K22 HG000044 / HG / NHGRI NIH HHS / United States
U01 HG007919 / HG / NHGRI NIH HHS / United States
RM1 HG006193 / HG / NHGRI NIH HHS / United States