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Related Concept Videos

Chromatin Modification in iPS Cells01:32

Chromatin Modification in iPS Cells

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Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (iPS) cells.
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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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Inheritance of Chromatin Structures03:17

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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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The histone proteins in the nucleosomes are post-translationally modified (PTM) to increase or decrease access to DNA. The commonly observed PTMs are methylation, acetylation, phosphorylation, and ubiquitination of lysine amino acids in the histone H3 tail region. These histone modifications have specific meaning for the cell. Hence, they are called "histone code". The protein complex involved in histone modification is termed as "reader-writer" complex.
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In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
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Heterochromatin02:38

Heterochromatin

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The extent of chromatin compaction can be studied by staining chromatin using specific DNA binding dyes. Under the microscope, the dense-compacted regions that take up more dye are called heterochromatin. Heterochromatin is further classified into two forms – constitutive heterochromatin and facultative heterochromatin.
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A Chromatin Assay for Human Brain Tissue
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Chromatin accessibility during human first-trimester neurodevelopment.

Camiel C A Mannens1, Lijuan Hu1, Peter Lönnerberg1

  • 1Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Solna, Sweden.

Nature
|May 1, 2024
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Summary
This summary is machine-generated.

This study maps chromatin accessibility and gene expression in the developing human brain during early development. It reveals gene regulatory mechanisms and identifies specific neuron types vulnerable to neurodevelopmental disorder mutations.

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Area of Science:

  • Neuroscience
  • Genomics
  • Developmental Biology

Background:

  • Human brain development involves complex gene regulation via transcription factors and chromatin accessibility.
  • Previous studies lacked comprehensive chromatin accessibility atlases for the entire developing brain, particularly in the first trimester.
  • Single-cell gene expression atlases exist, but paired chromatin accessibility data across the whole developing brain is limited.

Purpose of the Study:

  • To create a comprehensive atlas of chromatin accessibility and paired gene expression across the entire developing human brain during the first trimester.
  • To identify gene regulatory elements and their target genes involved in early neurodevelopment.
  • To investigate the genetic underpinnings of neurodevelopmental disorders by linking genetic variations to regulatory elements.

Main Methods:

  • Generated multiomic data (chromatin accessibility and gene expression) from the developing human brain (6-13 weeks post-conception).
  • Defined 135 distinct cell clusters and linked cis-regulatory elements to gene expression.
  • Employed convolutional neural networks to identify transcription factor-binding sites and analyzed disease-associated single nucleotide polymorphisms.

Main Results:

  • Mapped chromatin accessibility and gene expression across the entire developing human brain in the first trimester.
  • Observed an increase in accessible regions with developmental age and neuronal differentiation.
  • Identified specific neuronal subtypes, like midbrain GABAergic neurons, vulnerable to mutations linked to major depressive disorder.

Conclusions:

  • Provides a detailed reference for gene regulatory mechanisms in early human brain development.
  • Links specific regulatory elements and transcription factors to neuronal subtype specification.
  • Highlights the potential of chromatin accessibility mapping for understanding neurodevelopmental disorders and identifying vulnerable cell populations.