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Active opsin loci adopt intrachromosomal loops that depend on the photoreceptor transcription factor network
- Peng, Guang-Hua, Chen, Shiming
- Proceedings of the National Academy of Sciences of the United States of America 2011 v.108 no.43 pp. 17821-17826
- essential genes, gene expression, humans, leucine zipper, loci, mice, photoreceptors, retina, rhodopsin, transcription factors
- Rod and cone opsin genes are expressed in a mutually exclusive manner in their respective photoreceptor subtypes in the mammalian retina. Previous transgenic mouse studies showed that functional interactions between the distal enhancer and proximal promoter of rhodopsin and long/medium-wavelength (L/M) opsin genes are essential for regulating their cell-typeâspecific transcription. We have used chromosomal conformation capture assays in mouse retinas to investigate the molecular mechanism responsible for this interaction. Here we show that each opsin gene forms intrachromosomal loops in the appropriate photoreceptor subtype, while maintaining a linear configuration in other cell types where it is silent. The enhancer forms physical contacts not only with the promoter but also with the coding regions of each opsin locus. ChIP assays showed that cell-typeâspecific target binding by three key photoreceptor transcription factorsâconeârod homeobox (CRX), neural retina leucine zipper (NRL), and nuclear receptor subfamily 2, group E, member 3 (NR2E3)âis required for the appropriate local chromosomal organization and transcription of rod and cone opsins. Similar correlations between chromosomal loops and active transcription of opsin genes were also observed in human photoreceptors. Furthermore, quantitative chromosomal conformation capture on human retinas from two male donors showed that the L/M enhancer locus control region (LCR) loops with either the L or M promoter in a near 3:1 ratio, supporting distance-dependent competition between L and M for LCR. Altogether, our results suggest that the photoreceptor transcription factor network cooperatively regulates the chromosomal organization of target genes to precisely control photoreceptor subtype-specific gene expression.