Epigenetic gene expression mechanism in light sensitive cells in the eye identified

Epigenetic gene expression mechanism in light sensitive cells in the eye identified

Mechanism for establishing retinal photoreceptor cell identity discovered

Sep 12, 2017Life Sciences & Medicine

There are photoreceptors, light sensitive cells, in the retina of vertebrates including humans. In humans, there are two types of photoreceptors: rods and cones. The cones are most sensitive to one of three different colors (green, red or blue) and the rods are most sensitive to light and dark changes. During the process of development, optical sensor proteins called ‘opsin’ with different wavelengths are expressed in three types of cone cells: red, green, and blue, as well as rod photoceptor cells, finalizing cell differentiation.

For example, red cone cells express red opsin only and rod photoreceptor cells express rod opsin only. In cones and rods, other than opsin, many different types of rod and cone photoreceptor proteins are expressed; however, the role of epigenetic regulation in photoreceptor cell gene expression has been poorly understood.

A group of researchers led by Associate Professor OMORI Yoshihiro, Graduate Student KUBO Shun, and Professor FURUKAWA Takahisa at the Institute for Protein Research, Osaka University, together with researchers from Nagoya University and RIKEN, clarified the epigenetic control system in retinal photoreceptor cells, demonstrating its importance in neural development.

It was not well-known whether the final differentiation of neuronal cells in the brain and retina is controlled by epigenetics. Epigenetic control is a mechanism for control and transmission of gene expression that is not caused by changes in DNA sequence and is deeply related to generation and differentiation of multicellular organisms and the onset of cancer and psychological disorders. It has been drawing attention as a mechanism for controlling the relationship between living organisms and their environment in recent years.

This group thought Sterile Alpha Motif Domain Containing 7 (Samd7) proteins, which are expressed in rod photoreceptor cells, were involved in epigenetic control, from their structure. They made Samd7-null mice and found that blue opsin, which is not supposed to be expressed in rod photoreceptor cells, was predominantly expressed and that the amount of original rod opsin in rod photoreceptor cells halved. Thus, rod photoreceptor cell dysfunction in Samd7-null mice was revealed. It is thought that Samd7-null mice have a condition similar to night blindness, or poor vision in low light in humans.

This group examined proteins that bond to Samd7, finding that an epigenetic repressive factor, polycomb repressive complex (PRC), bound to Samd7. The group also found that Samd7 regulated methylation and ubiquitination of histone and controlled at least 400 genes other than opsin, demonstrating that Samd7 played a critical role in establishing rod photoreceptor cell identity.

The study using knockout mice clarified that epigenetic control is necessary for establishing neuronal cell identities. This will become a big step toward the understanding of a mechanism behind the establishment of identities of retinal photoreceptor cells and neuronal cells.


Precise transcriptional regulation controlled by a transcription factor network is known to be crucial for establishing correct neuronal cell identities and functions in the CNS. In the retina, the expression of various cone and rod photoreceptor cell genes is regulated by multiple transcription factors; however, the role of epigenetic regulation in photoreceptor cell gene expression has been poorly understood. Here, we found that Samd7, a rod-enriched sterile alpha domain (SAM) domain protein, is essential for silencing nonrod gene expression through H3K27me3 regulation in rod photoreceptor cells. Samd7-null mutant mice showed ectopic expression of nonrod genes including S-opsin in rod photoreceptor cells and rod photoreceptor cell dysfunction. Samd7 physically interacts with Polyhomeotic homologs (Phc proteins), components of the Polycomb repressive complex 1 (PRC1), and colocalizes with Phc2 and Ring1B in Polycomb bodies. ChIP assays showed a significant decrease of H3K27me3 in the genes up-regulated in the Samd7-deficient retina, showing that Samd7 deficiency causes the derepression of nonrod gene expression in rod photoreceptor cells. The current study suggests that Samd7 is a cell type-specific PRC1 component epigenetically defining rod photoreceptor cell identity.

Figure 1 . Loss of Samd7 in mice affects establishment of retinal rod photoreceptor identity and causes dysfunction of rod photoreceptor cells.

Figure 2. Blue cone opsin is ectopically expressed in Samd7-null rod photoreceptor cells.

Figure 3. Samd7 regulates gene expression in rod photoreceptor cells through epigenetic machinery.

To learn more about this research, please view the full research report entitled " Samd7 is a cell type-specific PRC1 component essential for establishing retinal rod photoreceptor identity " at this page of the Proceedings of the National Academy of Sciences of the United States of America (PNAS) website.

Related link

Technical Glossary