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Related Concept Videos

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.
Constitutive heterochromatin: It is a highly compact region of chromatin that is mostly concentrated in the centromere and telomere. Unlike euchromatin, the amino acid at...
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Chromatin Position Affects Gene Expression02:35

Chromatin Position Affects Gene Expression

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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. 
Topologically Associated Domains (TADs)
The 3-dimensional positioning of chromatin in the nucleus influences the...
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Inheritance of Chromatin Structures03:17

Inheritance of Chromatin Structures

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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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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.
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
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Euchromatin01:01

Euchromatin

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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 take up more dye, appearing darker, while the less-compact areas take up less dye and appear lighter. Based on the compaction level, chromatins are classified into two primary forms – euchromatin and heterochromatin.
Euchromatin is the less dense region of the chromatin and stains lighter. Euchromatin contains histone H3 extensively...
7.1K
Position-effect Variegation02:32

Position-effect Variegation

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In 1928, a German botanist Emil Heitz observed the moss nuclei with a DNA binding dye. He observed that while some chromatin regions decondense and spread out in the interphase nucleus, others do not. He termed them euchromatin and heterochromatin, respectively. He proposed that the heterochromatin regions reflect a functionally inactive state of the genome. It was later confirmed that heterochromatin is transcriptionally repressed, and euchromatin is transcriptionally active chromatin.
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Differentiation of Atrial Cardiomyocytes from Pluripotent Stem Cells Using the BMP Antagonist Grem2
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Deciphering the chromatin spatial organization landscapes during BMMSC differentiation.

Zhaowei Teng1, Yun Zhu2, Da Lin3

  • 1Department of Orthopedics, The First People's Hospital of Yunnan Province, Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan 650032, China; Key Laboratory of Yunnan Provincial Innovative Application of Traditional Chinese Medicine, The First People's Hospital of Yunnan Province, Kunming, Yunnan 650032, China; Clinical Medical Research Center, The First People's Hospital of Yunnan Province, Kunming, Yunnan 650032, China.

Journal of Genetics and Genomics = Yi Chuan Xue Bao
|January 31, 2023
PubMed
Summary

Aging bone density diseases stem from imbalances in bone marrow mesenchymal stem cells (BMMSCs). This study maps BMMSC differentiation, revealing genetic links to osteoporosis and identifying potential drug targets.

Keywords:
ATAC-seqBone marrow mesenchymal stem cellsDifferentiationGenome-wide association studiesHi-CSingle nucleotide polymorphisms

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Area of Science:

  • Genomics
  • Epigenetics
  • Stem Cell Biology

Background:

  • Differentiation imbalance in bone marrow mesenchymal stem cells (BMMSCs) contributes to age-related bone density diseases.
  • The epigenetic and chromatin organization during BMMSC differentiation into osteoblasts and adipocytes is not well understood.

Purpose of the Study:

  • To systematically map the 4D genome and dynamic epigenetic atlas of BMMSCs during differentiation.
  • To identify genetic variations and regulatory elements associated with bone degeneration and osteoporosis.

Main Methods:

  • RNA sequencing
  • Assay for Transposase-Accessible Chromatin sequencing (ATAC-seq)
  • High-throughput chromosome conformation capture (Hi-C)
  • Multi-omics analysis integrating genome-wide association studies (GWAS) and expression quantitative trait loci (eQTL) data.

Main Results:

  • Analysis revealed distinct chromatin loop structures during BMMSC differentiation.
  • Identified 274 genes and 3634 single nucleotide polymorphisms (SNPs) linked to bone degeneration and osteoporosis.
  • Discovered 26 motifs, 260 transcription factors (TFs), and 291 SNPs influencing eQTLs.
  • DAAM2, TIMP2, and TMEM241 were identified as key genes in bone diseases.

Conclusions:

  • The study provides a comprehensive epigenetic and 4D genome atlas of BMMSC differentiation.
  • Identified specific genes and SNPs associated with osteoporosis, offering insights into disease mechanisms.
  • DAAM2, TIMP2, and TMEM241 represent potential therapeutic targets for bone degeneration and osteoporosis.