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Locus control region function and heterochromatin-induced position effect variegation

R Festenstein1, M Tolaini, P Corbella

  • 1Division of Molecular Immunology, National Institute for Medical Research, The Ridgeway, London, UK.

Science (New York, N.Y.)
|February 23, 1996
PubMed
Summary
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Human CD2 locus control regions (LCRs) are vital for maintaining open chromatin structures. These sequences prevent variegated gene expression, even in centromeric positions, ensuring consistent gene function.

Area of Science:

  • Molecular Biology
  • Genetics
  • Epigenetics

Background:

  • Gene expression regulation is crucial for cellular function.
  • Chromatin structure plays a significant role in controlling gene accessibility.
  • Locus control regions (LCRs) are known to influence the expression of specific genes.

Purpose of the Study:

  • To investigate the role of human CD2 locus control region (LCR) sequences in establishing and maintaining an open chromatin configuration.
  • To determine if LCRs are essential for preventing variegated gene expression.

Main Methods:

  • Generation of transgenic mice carrying an hCD2 mini-gene.
  • Integration of the transgene in different genomic locations, including centromeric regions.
  • Analysis of gene expression patterns (variegation) in the presence or absence of specific LCR sequences.

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Main Results:

  • Transgenes with only the 3' enhancer showed variegated expression when integrated in centromeric positions.
  • Transgenes including additional 3' sequences (LCRs) exhibited no variegation, irrespective of integration site.
  • A short region lacking enhancer activity was identified as crucial for chromatin domain stability.

Conclusions:

  • Human CD2 LCR sequences are essential for establishing and maintaining an open chromatin configuration.
  • LCRs prevent variegated gene expression by ensuring a stable, open chromatin domain.
  • A non-enhancer sequence within the LCR is critical for chromatin domain regulation.