ChIP-seq of plasma cell-free nucleosomes identifies gene expression programs of the cells of origin.

Cell-Free System Chromatin Immunoprecipitation Colorectal Neoplasms / genetics Enhancer Elements, Genetic / genetics Gene Expression Regulation, Neoplastic Hepatocytes / metabolism Humans Neoplasm Metastasis Nucleosomes / genetics Promoter Regions, Genetic / genetics Sequence Analysis, DNA / methods

Journal

Nature biotechnology

ISSN: 1546-1696

Titre abrégé: Nat Biotechnol

Pays: United States

ID NLM: 9604648

Informations de publication

Date de publication:
05 2021

Historique:

received: 20 09 2019

accepted: 17 11 2020

pubmed: 13 1 2021

medline: 29 6 2021

entrez: 12 1 2021

Statut: ppublish

Résumé

Cell-free DNA (cfDNA) in human plasma provides access to molecular information about the pathological processes in the organs or tumors from which it originates. These DNA fragments are derived from fragmented chromatin in dying cells and retain some of the cell-of-origin histone modifications. In this study, we applied chromatin immunoprecipitation of cell-free nucleosomes carrying active chromatin modifications followed by sequencing (cfChIP-seq) to 268 human samples. In healthy donors, we identified bone marrow megakaryocytes, but not erythroblasts, as major contributors to the cfDNA pool. In patients with a range of liver diseases, we showed that we can identify pathology-related changes in hepatocyte transcriptional programs. In patients with metastatic colorectal carcinoma, we detected clinically relevant and patient-specific information, including transcriptionally active human epidermal growth factor receptor 2 (HER2) amplifications. Altogether, cfChIP-seq, using low sequencing depth, provides systemic and genome-wide information and can inform diagnosis and facilitate interrogation of physiological and pathological processes using blood samples.

Identifiants

DOI: 10.1038/s41587-020-00775-6 PMID: 33432199 PMC: PMC7610786

pubmed: 33432199

doi: 10.1038/s41587-020-00775-6

pii: 10.1038/s41587-020-00775-6

pmc: PMC7610786

mid: EMS114933

doi:

Substances chimiques

Nucleosomes 0

Types de publication

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

Langues

eng

Sous-ensembles de citation

Pagination

586-598

Subventions

Organisme : European Research Council

ID : 340712

Pays : International

Organisme : NCI NIH HHS

ID : R01 CA197081

Pays : United States

Organisme : NHGRI NIH HHS

ID : RM1 HG006193

Pays : United States

Commentaires et corrections

Type : ErratumIn

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