Author response: The preRC protein ORCA organizes heterochromatin by assembling histone H3 lysine 9 methyltransferases on chromatin
Year: 2015
Type: peer-review
Abstract: The genetic material inside cells is contained within molecules of DNA. In animals and other eukaryotes, the DNA is tightly wrapped around proteins called histones to form a compact structure known as chromatin. There are two forms of chromatin: loosely packed chromatin tends to contain genes that are highly active in cells, while tightly packed chromatin—called heterochromatin—tends to contain less-active genes. How tightly DNA is packed in chromatin can be changed by adding small molecules known as methyl tags to individual histone proteins. Enzymes called KMTs are responsible for attaching these methyl tags to a specific site on the histones. Before a cell divides, it duplicates its DNA and these methyl tags, so that they can be passed onto the newly formed cells. This enables the new cells to ‘remember’ which genes were inactive or active in the original cell. A protein known as ORCA associates with heterochromatin, but it is not clear what role it plays in controlling the structure of chromatin. Giri et al. studied ORCA and the KMTs in human cells. The experiments show that ORCA recognizes the methyl tags and binds to the KMTs in regions of heterochromatin, but not in regions where the DNA is more loosely packed. Next, Giri et al. used a technique called single-molecule pull-down, which is able to identify individual proteins within a group. These experiments showed that several KMT enzymes can bind to a single ORCA protein at the same time. ORCA stabilizes the binding of KMTs to chromatin, which enables the KMTs to modify the histones within it. Cells lacking ORCA had fewer methyl tags on their histones, which altered the structure of the chromatin. This also affected the timing with which DNA copying takes place in cells before the cell divides. Giri et al.'s findings suggest that ORCA acts as a scaffold for the KMTs and that its activity at specific sites on chromatin is important for the organization of heterochromatin. The next step is to identify the exact regions in the genome where the timing of DNA copying is regulated by ORCA.
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
OpenAlex ID: W2988823409