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Inheritance of Chromatin Structures

Inheritance of Chromatin Structures

Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying...

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2D and 3D Human Induced Pluripotent Stem Cell-Based Models to Dissect Primary Cilium Involvement during Neocortical Development

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Cell-type-specific 3D epigenomes in the developing human cortex.

Michael Song^1,2, Mark-Phillip Pebworth^3,4, Xiaoyu Yang¹

¹Institute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.

|October 15, 2020

Summary

This summary is machine-generated.

This study maps cell-type-specific gene regulation in the developing human brain, revealing how chromatin interactions fine-tune gene expression for lineage specification. A new CRISPRview technique validates these regulatory elements in complex cell mixtures.

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Area of Science:

Neuroscience
Genomics
Developmental Biology

Background:

Studying human corticogenesis is challenging due to limited samples and tissue complexity.
Previous research identified numerous cell types and subtypes in the developing cortex.

Purpose of the Study:

To characterize cell-type-specific epigenomic features in the human cortex.
To investigate the role of cis-regulatory chromatin interactions in gene regulation and lineage specification.
To develop a novel method for validating regulatory elements in primary cells.

Main Methods:

Isolation of specific cell types (radial glia, progenitor cells, neurons) from mid-gestational human cortex.
Analysis of cell-type-specific chromatin interactions, open chromatin, and transcriptomes.
Development and application of CRISPRview for validating cis-regulatory elements.

Main Results:

Chromatin interactions are crucial for gene regulation, with specific enrichment of transposable elements and disease variants.
Super-interactive promoters, showing high chromatin interactivity, are linked to lineage-specific genes.
CRISPRview successfully validated cell-type-specific cis-regulatory elements in heterogeneous primary cell populations.

Conclusions:

Epigenomic changes, particularly chromatin interactions, play a key role in human corticogenesis and lineage specification.
The findings offer insights into cell-type-specific gene expression during human brain development.
CRISPRview provides a powerful tool for studying gene regulation in complex primary cell systems.