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Cytosine methylation is a repressive, epigenetically propagated DNA modification. Although patterns of DNA methylation seem tightly regulated in mammals, it is unclear how these are specified and to what extent this process entails genetic or epigenetic regulation. To dissect the role of the underlying DNA sequence, we sequentially inserted over 50(More)
CTCF sites are abundant in the genomes of diverse species but their function is enigmatic. We used chromosome conformation capture to determine long-range interactions among CTCF/cohesin sites over 2 Mb on human chromosome 11 encompassing the beta-globin locus and flanking olfactory receptor genes. Although CTCF occupies these sites in both erythroid K562(More)
Chromatin loops juxtapose distal enhancers with active promoters, but their molecular architecture and relationship with transcription remain unclear. In erythroid cells, the locus control region (LCR) and β-globin promoter form a chromatin loop that requires transcription factor GATA1 and the associated molecule Ldb1. We employed artificial zinc fingers(More)
Long-range interactions between distant regulatory elements, such as enhancers, and their target genes underlie the specificity of gene expression in many developmentally regulated gene families. NLI/Ldb1, a widely expressed nuclear factor, is a potential mediator of long-range interactions. Here, we show that NLI/Ldb1 and erythroid-binding partners(More)
Distal enhancers commonly contact target promoters via chromatin looping. In erythroid cells, the locus control region (LCR) contacts β-type globin genes in a developmental stage-specific manner to stimulate transcription. Previously, we induced LCR-promoter looping by tethering the self-association domain (SA) of Ldb1 to the β-globin promoter via(More)
Transcription activation of a gene involves the ordered recruitment of components of the basal transcription machinery in concert with alterations in chromatin structure, including nucleosome remodeling and post-translational modification of histones. Enhancers and locus control regions (LCRs) that are remote from the genes they activate, recruit the(More)
Previous studies have shown that the major metabolic resistance locus in the insecticide-resistant Drosophila line Rst(2)DDT(Wisconsin) maps between the markers cn and vg on chromosome 2. Six cytochrome P450 genes exist in this region. We investigated the expression levels of these P450 genes in DDT-resistant and -susceptible fly lines. We report: (i) DDT(More)
The mechanism underlying enhancer-blocking by insulators is unclear. We explored the activity of human beta-globin HS5, the orthologue of the CTCF-dependent chicken HS4 insulator. An extra copy of HS5 placed between the beta-globin locus control region (LCR) and downstream genes on a transgene fulfills the classic predictions for an enhancer-blocker.(More)
It is estimated that the human genome contains hundreds of thousands of enhancers, so understanding these gene-regulatory elements is a crucial goal. Several fundamental questions need to be addressed about enhancers, such as how do we identify them all, how do they work, and how do they contribute to disease and evolution? Five prominent researchers in(More)
The yeast alpha 2 repressor suppresses expression of a-mating-type-specific genes in haploid alpha and diploid a/alpha cell types. We inserted the alpha 2-binding site into the multicopy TRP1/ARS1 yeast plasmid and examined the effects of alpha 2 on the chromatin structure of the derivative plasmids in alpha cells, and a/alpha cells. Whereas no effect on(More)