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Letter

Domain-wide regulation of gene expression in the human genome

¹ Department of Human Genetics, Academic Medical Centre, University of Amsterdam, 1100 DE Amsterdam, The Netherlands; ² Swammerdam Institute for Life Sciences, University of Amsterdam, 1100 DE Amsterdam, The Netherlands; ³ AMC Liver Centre, 1105 BK Amsterdam, The Netherlands

Transcription factor complexes bind to regulatory sequences of genes, providing a system of individual expression regulation. Targets of distinct transcription factors usually map throughout the genome, without clustering. Nevertheless, highly and weakly expressed genes do cluster in separate chromosomal domains with an average size of 80–90 genes. We therefore asked whether, besides transcription factors, an additional level of gene expression regulation exists that acts on chromosomal domains. Here we show that identical green fluorescent protein (GFP) reporter constructs integrated at 90 different chromosomal positions obtain expression levels that correspond to the activity of the domains of integration. These domains are up to 80 genes long and can exert an eightfold effect on the expression levels of integrated genes. 3D-FISH shows that active domains of integration have a more open chromatin structure than integration domains with weak activity. These results reveal a novel domain-wide regulatory mechanism that, together with transcription factors, exerts a dual control over gene transcription.

⁵ Corresponding author.

E-mail r.versteeg{at}amc.uva.nl; fax 31-20-6918626.

[Supplemental material is available at www.genome.org. The microarray data from this study have been submitted to GEO under accession no. GSE6629. Sequences of all integration sites were submitted to GenBank under accession nos. EF214748–EF214837.]

Article published online before print. Article and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.6276007

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