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CRISPR-Mediated Reorganization of Chromatin Loop Structure
Published on: September 14, 2018
Transcriptional interference among the murine beta-like globin genes
Xiao Hu1, Susan Eszterhas, Nicolas Pallazzi
1Department of Microbiology/Immunology and Norris Cotton Cancer Center, Dartmouth Medical School, Hanover, NH 03756, USA.
Blood
|November 2, 2006
Summary
Deleting embryonic globin gene promoters in mice altered beta-like gene expression. This suggests direct transcriptional interference, not locus control region competition, influences gene regulation during development.
Area of Science:
- Genetics
- Developmental Biology
- Molecular Biology
Background:
- Mammalian beta-globin loci feature multiple genes with stage-specific activation.
- Gene transcription within a locus can impact other genes in the same locus.
- A prevailing theory suggests competition for locus control region (LCR) activity explains transcriptional interference.
Purpose of the Study:
- To investigate how murine embryonic globin gene transcription influences other beta-like genes.
- To test the locus control region (LCR) competition model versus direct transcriptional interference.
Main Methods:
- Generated mice with deleted promoter regions of embryonic Ey and betah1 genes.
- Measured the transcription of remaining beta-like globin genes during primitive erythropoiesis.
- Performed protein analysis to confirm betah0 globin protein production.
Main Results:
- Deletion of Ey and betah1 promoters increased betamajor and betaminor transcription 2-3 fold.
- Ey deletion uniquely activated betah0 transcription, a gene downstream of Ey.
- No transcriptional interference was observed between Ey and betah1, contradicting LCR competition.
Conclusions:
- Direct transcriptional interference from Ey suppresses betah0 expression.
- The findings challenge the LCR competition model for embryonic beta-like globin gene regulation.
- betah0 encodes a translatable protein capable of pairing with alpha globin.
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