Also, it has been the base for the discovery of all classes of cis-regulatory elements including promoters, enhancers, insulators, silencers and locus control regions.

These areas of hypersensitivity are now shown to be functionally important in vivo, as they mark regions which comprise a putative locus control region (LCR).

Expression of all of these genes is controlled by single locus control region (LCR), and the genes are differentially expressed throughout development.

Expression of beta globin and the neighboring globins in the β-globin locus is controlled by single locus control region (LCR).

After this first report, locus control regions have now been identified for many genes and have permitted for example the ectopic expression of genes in transgenic mice.

The protein encoded by this gene contains a paired-like homeodomain and binds to the core of the locus control region of the red/green visual pigment gene cluster.

Locus control regions (LCR) are defined by their ability to enhance the expression of linked genes to physiological levels in a tissue-specific and copy number-dependent manner at ectopic chromatin sites.

By using the globin gene cluster he made the ground-breaking discovery of a locus control region located upstream of the gene itself and governing overall control of globin gene expression.

Sometimes the genes coding fetal isoforms occur adjacent to their adult homologues in the genome, and in those cases a locus control region often coordinates the transition from fetal to adult forms.

The evidence in this paper for the class II MHC Ea gene supports the view that, in principle, all tissue specific genes/multigene families would have a 'locus control region' as presently defined.

This problem has recently begun to be addressed by utilizing zinc finger nucleases or by including certain sequences such as the beta-globin locus control region to direct the site of integration to specific chromosomal sites.

These locus control regions (LCR) were first defined for the β-globin system (14,15) and their ability to orchestrate lineage specific expression of sequences linked in cis has made them key elements in the development of gene therapy technology.

We discuss whether the regions containing these apparently developmentally programmed patterns of DNase I hypersensitive sites reflect the action of a locus control region (LCR) by conferring tissue-specific, position-independent, copy-dependent expression on a wild-type Ea gene.

However, this definition has changed to define cis-regulatory modules as a DNA sequence with transcription factor binding sites which are clustered into modular structures, including -but not limited to- locus control regions, promoters, enhancers, silencers, boundary control elements and other modulators.

Whether this includes a combination of enhancer-type elements which overcomes any 'silencing' effects of the surrounding chromatin on the integrated transgene, and/or elements which interact with the nuclear matrix directly to isolate the transgene from inactive chromatin (54-56), needs further analysis of potential locus control regions.

To determine whether the Ea DH groups I-V define a functionally important chromatin domain or locus control region (LCR), we have used wild type Ea d gene constructs to generate transgenic mouse lines from strains that do not express an endogenous Ea gene product.

Finally, we have shown here that DNase I hypersensitivity sites can be used to pinpoint interesting regions of specific importance to the expression of the class II MHC Ea gene, both as composing part of a locus control region, and as possible markers for B cell commitment.