{"id":14583,"date":"2024-12-05T15:55:48","date_gmt":"2024-12-05T20:55:48","guid":{"rendered":"https:\/\/www.med.unc.edu\/genetics\/?p=14583"},"modified":"2024-12-05T15:55:48","modified_gmt":"2024-12-05T20:55:48","slug":"unc-scientists-discover-new-details-of-gene-regulation","status":"publish","type":"post","link":"https:\/\/www.med.unc.edu\/genetics\/unc-scientists-discover-new-details-of-gene-regulation\/","title":{"rendered":"黑料网 Scientists Discover New Details of Gene Regulation"},"content":{"rendered":"

A research team led by Daniel McKay, PhD, associate professor in the Departments of Biology and Genetics, has identified a key focal point in the biological processes that control cell identity and can lead to disease when mutated.<\/p>\n

\n
\"Daniel<\/a>
Daniel McKay, PhD<\/figcaption><\/figure>\n

Genes make up the blueprints and outline the process of building every living organism.<\/p>\n

To ensure that the right genes are activated in the right cells, and in the right amounts at the right time, genes are constantly being regulated by small molecular machines made of proteins. When gene regulation fails, or specific genes are altered through mutation, the body is more predisposed to diseases such as cancer, Alzheimer\u2019s, and autoimmune disorders.<\/p>\n

Now, for the first time in animals, the lab of\u00a0Daniel McKay, PhD<\/a>, associate professor of Biology in the 黑料网 College of Arts and Sciences and of Genetics at the 黑料网, has identified a crucial focal point in the regulatory processes that govern cell identity.<\/p>\n

Researchers discovered that a chemical alteration on a single protein, histone H3, is essential for controlling the genes that help cells remember their own identity and function. When the genes and proteins in charge of keeping these regulatory processes in check are mutated, cells will proliferate out of control or resist cell death pathways, two key features of cancer.<\/p>\n

Their results\u00a0were published<\/a>\u00a0in\u00a0Genes and Development<\/em>. Cyril Anyetei-Anum, a PhD candidate in the Curriculum in Genetics and Molecular Biology and member of the McKay lab, was lead author on the study.<\/p>\n

The Importance of Gene Expression and Chemical Modifications of Histones<\/strong><\/p>\n

Our genomes are huge. Each cell contains over 6-billion DNA letters, that, if stretched out end-to-end, would measure 2-meters long. Small proteins called histones are tasked with tightly packaging all of that DNA into every cell, like a librarian shoving books into a full bookcase. Histones also play key roles in gene regulation.<\/p>\n

\"\"
Histone proteins (gray) wrapping up DNA (black) like a spool. Histones have short, protruding protein \u201ctails.\u201d Chemical modifications placed on these tails play key roles in gene regulation. The location of histone H3 lysine-4 is indicated with a green star.<\/figcaption><\/figure>\n

Small chemical modifications can be added to histones, which allow proteins to access the tightly bound DNA from their histone bookcases to turn \u201con\u201d and \u201coff\u201d genes in the organism. With ready access to DNA information, the body can carry out gene expression or convert genetic information into protein products that carry out actions specified in the DNA code.<\/p>\n

Scientists have long studied the processes that underlie gene expression and the chemical modifications of histones because of the downstream effects they have on cellular processes.<\/p>\n

One regulatory process of scientific interest is called epigenetic gene regulation. During this regulatory process, genes are altered in a \u201csilent\u201d manner, in that the genes are turned \u201con\u201d or \u201coff\u201d without physically altering the DNA code. Scientists are intensely focused on epigenetic gene regulation because drugs can be developed to target specific histone modifications and switch specific genes \u201con\u201d and \u201coff\u201d.<\/p>\n

Methylation is one of the more prevalent chemical modifications that histones undergo. Researchers have previously found that the methylation of one particular location, lysine-4, on histone H3, is closely correlated with turning genes \u201con.\u201d<\/p>\n

Knowing that this relationship exists, researchers have built a hypothesis that histone H3 lysine-4 methylation is required for gene activation. However, it has been surprisingly difficult for researchers to test this hypothesis because the genetic tools did not yet exist to test H3 lysine-4 methylation in animals.<\/p>\n

Evaluating Histone H3 lysine-4 Methylation in Animals<\/strong><\/p>\n

Over the past 10 years, the McKay lab has been collaborating with several labs at the University of North Carolina at Chapel Hill to create an experimental animal model system they could use to study the role of histone proteins in regulating genes.<\/p>\n

For this study, researchers examined\u00a0Drosophila melanogaster<\/em>, colloquially known as the fruit fly, because of its simple genetics and the fact that its genetic elements are incredibly similar to that of humans. With\u00a0Drosophila<\/em>\u00a0as their animal model, McKay and colleagues first determined that the methylation of histone H3 lysine-4 is required for the activation of \u201cmaster regulator\u201d genes.<\/p>\n

These genes are critical in the large-scale regulation of the early human body, including those that develop tissue and organ systems, produce specialized cells from stem cells, and aid cells in remembering their own identity and function.<\/p>\n

If these genes are expressed at the wrong time or place, they can transform cells from one identity into another, which is one of the key features of diseases like cancer. Due to the distinctive power of these genes, their expression is tightly controlled, and layers of mechanisms exist to ensure they are turned \u201con\u201d and kept \u201coff\u201d in the right times and places inside animals.<\/p>\n

In addition to finding that H3 lysine-4 methylation is important for activation of master regulator genes, McKay and colleagues also found that it plays a key role in turning \u201coff\u201d the protein machines that silence master regulator genes. These gene silencing proteins, referred to as Polycomb complexes, play critical roles in helping cells remember their own identity.<\/p>\n

Gene Silencing and Cancer<\/strong><\/p>\n

While every type of cell in our body expresses a specific set of genes that are required for its specialized role in the body, the cells are also using Polycomb complexes to \u201csilence\u201d genes that are not important for their predetermined role(s) at the same time.<\/p>\n

When Polycomb complexes are turned \u201coff\u201d, impacted cells \u201cforget\u201d their identity and acquire new properties, like proliferating out of control or resisting cell death pathways, two key features of cancer cells. The findings suggest that drugs targeting histone H3 lysine-4 methylation may be effective in counteracting the effects of Polycomb mutations found in human diseases.<\/p>\n

 <\/p>\n

This article originally appeared in 黑料网’s Vital Signs HERE<\/a>.<\/p>\n","protected":false},"excerpt":{"rendered":"

A research team led by Daniel McKay, PhD, associate professor in the Departments of Biology and Genetics, has identified a key focal point in the biological processes that control cell identity and can lead to disease when mutated.<\/p>\n","protected":false},"author":28418,"featured_media":10543,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":"","_links_to":"","_links_to_target":""},"categories":[2],"tags":[59],"class_list":["post-14583","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-news","tag-mckay","odd"],"acf":[],"yoast_head":"\n黑料网 Scientists Discover New Details of Gene Regulation | Department of Genetics<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" 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