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Related Concept Videos

Chromatin Immunoprecipitation- ChIP02:36

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Chromatin immunoprecipitation, or ChIP, is an antibody-based technique used to identify sites on DNA that bind to transcription factors of interest or histone proteins. It also helps determine the type of histone modifications such as acetylation, phosphorylation, or methylation.
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Chromatin is the massive complex of DNA and proteins packaged inside the nucleus. The complexity of chromatin folding and how it is packaged inside the nucleus greatly influences  access to genetic information. Generally, the nucleus' periphery is considered transcriptionally repressive, while the cell's interior is considered a transcriptionally active area. 
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Related Experiment Video

Updated: Jan 14, 2026

Author Spotlight: Nuclei Isolation from Mouse Cardiac Progenitor Cells for Epigenome and Gene Expression Profiling at Single-Cell Resolution
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Single-nucleus chromatin accessibility and gene expression co-profiling by ISSAAC-seq.

Wei Xu1,2, Yukun Hu3, Yunlong Zhang3

  • 1GMU-GIBH Joint School of Life Sciences, The Guangdong-Hong Kong-Macao Joint Laboratory for Cell Fate Regulation and Diseases, Guangzhou Medical University, Guangdong, China. xuwei2023@gzhmu.edu.cn.

Nature Protocols
|January 12, 2026
PubMed
Summary
This summary is machine-generated.

We developed ISSAAC-seq, a method for simultaneous chromatin accessibility and gene expression measurement in single nuclei. This technique enhances cellular heterogeneity studies by providing comprehensive molecular profiling.

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Area of Science:

  • Molecular Biology
  • Genomics
  • Epigenetics

Background:

  • Multimodal single-cell profiling offers deeper insights into cellular heterogeneity than single-modality approaches.
  • Co-detection of chromatin accessibility and gene expression is crucial for understanding cell type-specific gene regulation.

Purpose of the Study:

  • To introduce a sensitive and robust protocol, ISSAAC-seq, for concurrent measurement of chromatin accessibility and gene expression from the same single nucleus.
  • To enable comprehensive characterization of cellular heterogeneity and gene regulatory mechanisms.

Main Methods:

  • ISSAAC-seq involves dual Tn5 tagging of open chromatin regions and RNA-cDNA hybrids in bulk nuclei.
  • Single-nucleus isolation is achieved using various strategies, including plate and droplet barcoding.
  • The protocol is modular, supporting throughputs from hundreds to tens of thousands of nuclei.

Main Results:

  • High-quality data were generated for both chromatin accessibility and gene expression modalities.
  • The workflow is rapid, completable within 1–2 days.
  • The protocol demonstrates compatibility with multiple single-nucleus isolation and barcoding platforms.

Conclusions:

  • ISSAAC-seq provides a powerful tool for multimodal single-nucleus profiling.
  • The method facilitates the investigation of cell type-resolved gene regulatory mechanisms.
  • Its flexibility and efficiency make it suitable for diverse single-cell genomics applications.