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Isolation and Cultivation of Neural Progenitors Followed by Chromatin-Immunoprecipitation of Histone 3 Lysine 79 Dimethylation Mark
Published on: January 26, 2018
Complex developmental patterns of histone modifications associated with the human beta-globin switch in primary cells
Mei Hsu1, Christine A Richardson, Emmanuel Olivier
1Department of Microbiology and Immunology, and Norris Cotton Cancer Center, Dartmouth Medical School, Hanover, NH 03756, USA.
Experimental Hematology
|May 23, 2009
Summary
Histone modifications regulate gene expression. This study found distinct patterns of histone modifications across the beta-globin locus in erythroblasts, identifying active suppression of gamma genes in bone marrow cells.
Area of Science:
- Epigenetics
- Molecular Biology
- Hematopoiesis
Background:
- The beta-globin switch, crucial for red blood cell development, is not fully understood.
- Histone modifications are key regulators of gene expression.
- Understanding these mechanisms can inform treatments for beta-hemoglobinopathies.
Purpose of the Study:
- To investigate the presence and distribution of three critical histone modifications across the beta-globin locus in erythroblasts.
- To correlate these modifications with different beta-like globin gene expression profiles.
- To explore the chromatin landscape associated with weak gamma gene expression for potential therapeutic induction.
Main Methods:
- Utilized uncultured primary fetal and bone marrow erythroblasts, along with human embryonic stem cell-derived erythroblasts.
- Employed chromatin immunoprecipitation with specific antibodies against modified histones.
- Quantified precipitated DNA using real-time polymerase chain reaction across 40 sites.
Main Results:
- Observed stage-specific differences in histone modification patterns.
- Highly expressed genes were located within large domains of activating marks (H3ac, H3K4me2).
- Moderately expressed genes showed these marks in their immediate vicinity.
- H3K9me2, a repressive mark, was found at epsilon and gamma genes in bone marrow cells, indicating active suppression.
Conclusions:
- Demonstrated complex patterns of histone modifications correlating with gene expression levels (high, moderate, unexpressed).
- Indicated that postnatal activation of gamma-globin genes likely necessitates broad histone modification within a large domain surrounding these genes.
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