Genome-wide analysis uncovers high frequency, strong differential chromosomal interactions and their associated epigenetic patterns in E2-mediated gene regulation.
BACKGROUND
An emerging Hi-C protocol has the ability to probe three-dimensional (3D) architecture and capture chromatin interactions in a genome-wide scale. It provides informative results to address how chromatin organization changes contribute to disease/tumor occurrence and progression in response to stimulation of environmental chemicals or hormones.


RESULTS
In this study, using MCF7 cells as a model system, we found estrogen stimulation significantly impact chromatin interactions, leading to alteration of gene regulation and the associated histone modification states. Many chromosomal interaction regions at different levels of interaction frequency were identified. In particular, the top 10 hot regions with the highest interaction frequency are enriched with breast cancer specific genes. Furthermore, four types of E2-mediated strong differential (gain- or loss-) chromosomal (intra- or inter-) interactions were classified, in which the number of gain-chromosomal interactions is less than the number of loss-chromosomal interactions upon E2 stimulation. Finally, by integrating with eight histone modification marks, DNA methylation, regulatory elements regions, ERα and Pol-II binding activities, associations between epigenetic patterns and high chromosomal interaction frequency were revealed in E2-mediated gene regulation.


CONCLUSIONS
The work provides insight into the effect of chromatin interaction on E2/ERα regulated downstream genes in breast cancer cells.
Department of Pathology, Oslo University Hospital - Norwegian Radium Hospital, Montebello, 0310 Oslo, Norway. junbai.wang@rr-research.no
Junbai
J
Wang
Xun
X
Lan
Pei-Yin
PY
Hsu
Hang-Kai
HK
Hsu
Kun
K
Huang
Jeffrey
J
Parvin
Tim H-M
TH
Huang
Victor X
VX
Jin
D002843:Chromatin / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D002877:Chromosomes, Human / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D044127:Epigenesis, Genetic / Q000187:drug effects*; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000378:metabolism; D004967:Estrogens / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000235:genetics*; D023281:Genomics; D006801:Humans; D061986:MCF-7 Cells
D002843:Chromatin; D047628:Estrogen Receptor alpha; D004967:Estrogens; D004958:Estradiol