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""The chicken Ig-�� locus is organized by three cell-type-specific genes and two ubiquitously expressed genes. B-cell-specific DNase I hypersensitive sites (DHS) in that locus, including three present inside the flanking gene, were grouped into six regions and deleted. The deletions decreased Ig-�� mRNA content to http://www.selleckchem.com/products/byl719.html parameters. Thus, the collaboration of the scattered regulatory regions was essential and sufficient not only for B-cell-specific transcription of the Ig-�� gene, but also for the conversion of epigenetic parameters. On the basis of the knock-in studies, we determined the regions involved in the conversion and maintenance of the epigenetic parameters. These scattered regulatory regions were limited in vicinity such as in an intron of the gene, in the intergenic regions and in the introns of a flanking gene. In vertebrate cells, chromatin of a committed or active gene and its flanking region has the following epigenetic features: (i) general sensitivity to DNase I (Weintraub & Groudine 1976; Hebbes et?al. 1994; Bulger et?al. 2003); (ii) formation of cell-type-specific DNase I hypersensitive http://www.selleckchem.com/products/BEZ235.html sites (DHSs) (Elgin 1988; Gross & Garrard 1988); (iii) core histone modifications such as acetylation and methylation specific for the active chromatin state, mostly at the N-terminal http://www.selleck.cn/products/gsk-j4-hcl.html tails (Berger 2007); (iv) the presence of histone variants such as H3.3 and H2AZ (Hake & Allis 2006; Eirin-Lopez & Ausio 2007); and (v) unmethylated CG dinucleotides in the promoter (Klose & Bird 2006; Weber & Schubeler 2007). To activate cell-type-specific genes in the process of differentiation, it is necessary to convert the epigenetic status of a gene and its flanking region from an inactive to an active state, as well as recruit transcriptional initiation complexes at the promoter. Regulatory regions that are involved in the initiation and maintenance of transcription and epigenetic conversion are thought to be scattered not only in the vicinity of the gene, but also inside a flanking gene or distant from the gene (Kleinjan & van Heyningen 2005; Palstra et?al. 2008). Basically, three models have been proposed for the transcription mechanism mediated by scattered regulatory regions: (i) the looping model (Ptashne 1986); (ii) the tracking model; and (iii) the linking model (Bulger & Groudine 1999; Dorsett 1999). With the use of chromosome conformation capture (3C) (Dekker et?al. 2002; Tolhuis et?al. 2002) and RNA-TRAP (Carter et?al. 2002) methods, scattered regulatory regions have been showed to spatially assemble together to form a special loop structure named the ��active chromatin hub�� (Tolhuis et?al.
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