HiChIRP reveals RNA-associated chromosome conformation

Maxwell R Mumbach; Jeffrey M Granja; Ryan A Flynn; Caitlin M Roake; Ansuman T Satpathy; Adam J Rubin; Yanyan Qi; Zhaozhao Jiang; Shadi Shams; Bryan H Louie; Jimmy K Guo; David G Gennert; M Ryan Corces; Paul A Khavari; Maninjay K Atianand; Steven E Artandi; Katherine A Fitzgerald; William J Greenleaf; Howard Y Chang

doi:10.1038/s41592-019-0407-x

HiChIRP reveals RNA-associated chromosome conformation

Nat Methods. 2019 Jun;16(6):489-492. doi: 10.1038/s41592-019-0407-x. Epub 2019 May 27.

Authors

Maxwell R Mumbach^#^{1

2}, Jeffrey M Granja^#^{1

3}, Ryan A Flynn¹, Caitlin M Roake^{4

5}, Ansuman T Satpathy^{1

6}, Adam J Rubin⁷, Yanyan Qi¹, Zhaozhao Jiang⁸, Shadi Shams¹, Bryan H Louie¹, Jimmy K Guo¹, David G Gennert^{1

2}, M Ryan Corces¹, Paul A Khavari⁷, Maninjay K Atianand⁹, Steven E Artandi⁴, Katherine A Fitzgerald⁸, William J Greenleaf^#^{10

11

12

13}, Howard Y Chang^#^{14

15

16

17}

Affiliations

¹ Center for Personal Dynamic Regulomes, Stanford University School of Medicine, Stanford, CA, USA.
² Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
³ Program in Biophysics, Stanford University School of Medicine, Stanford, CA, USA.
⁴ Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
⁵ Cancer Biology Program, Stanford University School of Medicine, Stanford, CA, USA.
⁶ Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
⁷ Program in Epithelial Biology, Stanford University School of Medicine, Stanford, CA, USA.
⁸ Program in Innate Immunity, University of Massachusetts Medical School, Worcester, MA, USA.
⁹ Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
¹⁰ Center for Personal Dynamic Regulomes, Stanford University School of Medicine, Stanford, CA, USA. wjg@stanford.edu.
¹¹ Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA. wjg@stanford.edu.
¹² Department of Applied Physics, Stanford University, Stanford, CA, USA. wjg@stanford.edu.
¹³ Chan Zuckerberg Biohub, San Francisco, CA, USA. wjg@stanford.edu.
¹⁴ Center for Personal Dynamic Regulomes, Stanford University School of Medicine, Stanford, CA, USA. howchang@stanford.edu.
¹⁵ Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA. howchang@stanford.edu.
¹⁶ Program in Epithelial Biology, Stanford University School of Medicine, Stanford, CA, USA. howchang@stanford.edu.
¹⁷ Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA, USA. howchang@stanford.edu.

^# Contributed equally.

Abstract

Modular domains of long non-coding RNAs can serve as scaffolds to bring distant regions of the linear genome into spatial proximity. Here, we present HiChIRP, a method leveraging bio-orthogonal chemistry and optimized chromosome conformation capture conditions, which enables interrogation of chromatin architecture focused around a specific RNA of interest down to approximately ten copies per cell. HiChIRP of three nuclear RNAs reveals insights into promoter interactions (7SK), telomere biology (telomerase RNA component) and inflammatory gene regulation (lincRNA-EPS).

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cells, Cultured
Chromatin / chemistry*
Chromatin / genetics*
Chromosomes
Embryonic Stem Cells / cytology
Embryonic Stem Cells / metabolism*
Gene Expression Regulation*
Genome
Mice
Promoter Regions, Genetic
RNA / chemistry*
RNA / genetics
RNA, Long Noncoding / genetics*
Telomerase / chemistry*
Telomerase / genetics

Substances

Chromatin
EPS long non-coding RNA, mouse
RNA, Long Noncoding
telomerase RNA
RNA
Telomerase

Abstract

Publication types

MeSH terms

Substances

Grants and funding