PMID- 29229825
OWN - NLM
STAT- MEDLINE
DCOM- 20180709
LR  - 20190420
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 114
IP  - 52
DP  - 2017 Dec 26
TI  - Network analysis identifies chromosome intermingling regions as regulatory 
      hotspots for transcription.
PG  - 13714-13719
LID - 10.1073/pnas.1708028115 [doi]
AB  - The 3D structure of the genome plays a key role in regulatory control of the 
      cell. Experimental methods such as high-throughput chromosome conformation 
      capture (Hi-C) have been developed to probe the 3D structure of the genome. 
      However, it remains a challenge to deduce from these data chromosome regions that 
      are colocalized and coregulated. Here, we present an integrative approach that 
      leverages 1D functional genomic features (e.g., epigenetic marks) with 3D 
      interactions from Hi-C data to identify functional interchromosomal interactions. 
      We construct a weighted network with 250-kb genomic regions as nodes and Hi-C 
      interactions as edges, where the edge weights are given by the correlation 
      between 1D genomic features. Individual interacting clusters are determined using 
      weighted correlation clustering on the network. We show that intermingling 
      regions generally fall into either active or inactive clusters based on the 
      enrichment for RNA polymerase II (RNAPII) and H3K9me3, respectively. We show that 
      active clusters are hotspots for transcription factor binding sites. We also 
      validate our predictions experimentally by 3D fluorescence in situ hybridization 
      (FISH) experiments and show that active RNAPII is enriched in predicted active 
      clusters. Our method provides a general quantitative framework that couples 1D 
      genomic features with 3D interactions from Hi-C to probe the guiding principles 
      that link the spatial organization of the genome with regulatory control.
CI  - Copyright (c) 2017 the Author(s). Published by PNAS.
FAU - Belyaeva, Anastasiya
AU  - Belyaeva A
AD  - Laboratory for Information and Decision Systems, Massachusetts Institute of 
      Technology, Cambridge, MA 02139.
AD  - Institute for Data, Systems, and Society, Massachusetts Institute of Technology, 
      Cambridge, MA 02139.
FAU - Venkatachalapathy, Saradha
AU  - Venkatachalapathy S
AD  - Mechanobiology Institute, National University of Singapore, Singapore 117411.
FAU - Nagarajan, Mallika
AU  - Nagarajan M
AD  - Mechanobiology Institute, National University of Singapore, Singapore 117411.
FAU - Shivashankar, G V
AU  - Shivashankar GV
AD  - Mechanobiology Institute, National University of Singapore, Singapore 117411.
AD  - Institute of Molecular Oncology, Italian Foundation for Cancer Research, Milan 
      20139, Italy.
FAU - Uhler, Caroline
AU  - Uhler C
AUID- ORCID: 0000-0002-7008-0216
AD  - Laboratory for Information and Decision Systems, Massachusetts Institute of 
      Technology, Cambridge, MA 02139; cuhler@mit.edu.
AD  - Institute for Data, Systems, and Society, Massachusetts Institute of Technology, 
      Cambridge, MA 02139.
LA  - eng
GR  - T32 GM087237/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20171211
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
SB  - IM
MH  - Animals
MH  - *Chromosomes, Human/genetics/metabolism
MH  - Humans
MH  - Sequence Analysis, DNA/*methods
MH  - Transcription, Genetic/*physiology
PMC - PMC5748172
OTO - NOTNLM
OT  - 3D FISH
OT  - Hi-C
OT  - chromosome intermingling
OT  - epigenetics
OT  - network and clustering analysis
COIS- The authors declare no conflict of interest.
EDAT- 2017/12/13 06:00
MHDA- 2018/07/10 06:00
PMCR- 2017/12/11
CRDT- 2017/12/13 06:00
PHST- 2017/12/13 06:00 [pubmed]
PHST- 2018/07/10 06:00 [medline]
PHST- 2017/12/13 06:00 [entrez]
PHST- 2017/12/11 00:00 [pmc-release]
AID - 1708028115 [pii]
AID - 201708028 [pii]
AID - 10.1073/pnas.1708028115 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2017 Dec 26;114(52):13714-13719. doi: 
      10.1073/pnas.1708028115. Epub 2017 Dec 11.