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The glandular epithelium is made of one or more epithelial cells modified to synthesize and secrete chemical substances. Glandular epithelia can be classified based on cell number. Unicellular glands have individual secretory cells scattered across the epithelial monolayer. In contrast, multicellular glands consist of a hollow tubular duct attached to the cluster of secretory cells located in the deep pockets.
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Histone variants are the histone proteins with structural and sequence variations. These variants may be regarded as “mutant” forms that replace their canonical histone counterparts in the nucleosomes. Specific post-translational modifications on the histone variants enable further chromatin complexity and regulate tissue-specific gene expression. The most common histone variants are from histone H2A, H2B, and linker histone H1 families. However, several variants of histone H3...
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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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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 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.
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Expression Analysis of Mammalian Linker-histone Subtypes
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Histone Variant H2A.J Is Enriched in Luminal Epithelial Gland Cells.

Christophe E Redon1, Zoe Schmal2, Gargi Tewary2

  • 1Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.

Genes
|November 27, 2021
PubMed
Summary

Histone H2A.J is a novel protein highly expressed in luminal epithelial cells and various cancers, particularly breast and prostate. Its depletion affects estrogen-responsive genes, suggesting a role in luminal-B breast cancer development.

Keywords:
H2AFJH2AJcancer biomarkerestrogen-responsive geneshistone variant H2A.Jluminal breast cancerluminal prostate cancer

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • Histone variants play crucial roles in gene regulation and cellular processes.
  • H2A.J (H2AFJ) is a mammalian-specific histone H2A variant with limited prior investigation.
  • Understanding histone variant function is key to deciphering complex biological mechanisms.

Purpose of the Study:

  • To investigate the expression pattern and cellular localization of the histone variant H2A.J in human and mouse tissues.
  • To determine the potential of H2A.J as a biomarker for specific cancer types.
  • To explore the functional role of H2A.J in cancer, particularly in relation to estrogen signaling.

Main Methods:

  • Immunohistochemistry was employed to analyze H2A.J protein localization across diverse human and mouse tissue samples.
  • Expression levels of H2A.J were assessed in various cancer cell lines, with a focus on luminal breast and prostate cancer cells.
  • Gene knockout of H2AFJ was performed in T47D luminal breast cancer cells to study downstream effects on gene expression.

Main Results:

  • H2A.J exhibited cell-type specific expression, with significant enrichment in the luminal epithelial cells of multiple glands (breast, prostate, pancreas, thyroid, stomach, salivary).
  • High H2A.J expression was observed in numerous carcinoma cell lines, especially those originating from luminal breast and prostate cancers.
  • Knockout of the H2AFJ gene in T47D cells led to decreased expression of several estrogen-responsive genes.

Conclusions:

  • H2A.J is a promising novel biomarker for identifying luminal epithelial cancers.
  • The findings suggest a potential tumorigenic role for H2A.J in luminal-B breast cancer, possibly mediated through its influence on estrogen-responsive gene expression.