{"id":110671,"date":"2025-05-18T03:16:18","date_gmt":"2025-05-18T03:16:18","guid":{"rendered":"https:\/\/www.europesays.com\/uk\/110671\/"},"modified":"2025-05-18T03:16:18","modified_gmt":"2025-05-18T03:16:18","slug":"red-light-green-light-how-huntingtons-disease-influences-genetic-traffic-lights-hdbuzz-2","status":"publish","type":"post","link":"https:\/\/www.europesays.com\/uk\/110671\/","title":{"rendered":"Red Light, Green Light: How Huntington\u2019s Disease Influences Genetic Traffic Lights – HDBuzz"},"content":{"rendered":"

\"SarahBy Dr Sarah Hernandez<\/a> May 15, 2025 Edited by Dr Rachel Harding<\/a><\/p>\n

For Huntington\u2019s disease (HD), a lot of attention goes to the genetic change that causes HD, but new research is shining a light on something else – our epigenome<\/a><\/strong>. The word literally means, \u201cabove\u201d the \u201cgenome<\/a>\u201d, or above the genetic code. It\u2019s a layer of chemical marks that are added to genes to regulate their activity. Think of the epigenome<\/a> like a traffic control system for our genes. It\u2019s responsible for deciding when a gene should \u201cgo\u201d (get activated) or \u201cstop\u201d (stay quiet). When things go awry, like in HD, that traffic system breaks down.<\/p>\n

Imagine a busy intersection – traffic is carefully orchestrated with different colored lights, telling drivers when to stop and when to go. If a signal turns yellow, drivers know that the light is in a transition between letting those cars go, and telling them to stop. These yellow lights are similar to what scientists call \u201cbivalent\u201d marks.<\/p>\n

\"Huntington\u2019sHuntington\u2019s disease causes genetic traffic signals to go haywire, turning lights green that should be red and causing a genetic traffic jam. <\/p>\n

Image credit: Aayush Srivastava<\/a><\/p>\n

Bivalent genes carry both activating signals (the green light) and repressive signals (the red light) at the same time – like a yellow traffic light. This allows the gene to be ready to turn on quickly when needed, but also to stay off when it\u2019s not. In HD, something goes wrong with these bivalent marks.<\/p>\n

A surprising finding from this new work, led by Karine Merienne from the University of Strasbourg in France, is that certain genes that are normally \u201cturned off\u201d are staying \u201con\u201d in the neurons<\/a> of mice that model HD. The repressive signal (the \u201cred light\u201d) is lost, and the gene becomes more likely to turn on, as if the green light is stuck on. This means that genes which generally stay quiet in brain cells can get activated when they shouldn\u2019t, potentially causing harm to the neuron<\/a>.<\/p>\n

Those stuck green signals are happening in genes that are involved in the early development of the brain. These are genes that help guide how a neuron<\/a> develops and what kind of neuron<\/a> it becomes. In a brain without HD, these genes are turned off after the brain develops, but in HD, they seem to be active for longer. <\/p>\n

This is similar to what others have recently found,<\/a> with data suggesting that HD may lead to genetic changes that cause certain brain cells to lose their identity, turning off genes that help define them as unique types of neurons<\/a>. Until now, we didn\u2019t really know how this might be happening.<\/p>\n

\u201c<\/b>Think of the epigenome like a traffic control system for our genes. It\u2019s responsible for deciding when a gene should \u201cgo\u201d (get activated) or \u201cstop\u201d (stay quiet). When things go awry, like in HD, that traffic system breaks down.<\/p>\n

\u201d<\/p><\/blockquote>\n

The changes defined by Karine\u2019s team were seen in HD mice, where developmental genes – key players in brain development – were activated in mature neurons<\/a>. These persistent green traffic signals can make them more accessible for activation, which researchers think could contribute to problems in how neurons<\/a> function.<\/p>\n

There are special molecular machines in the cell that normally help keep this process in check, two of which are called PRC1 and PRC2. These complexes act like traffic cops, ensuring that genes stay in their proper lanes – some genes should stay off, and others should be on at the right time. PRC1 and PRC2 usually help maintain the \u201cred light\u201d by placing repressive marks on genes, keeping them quiet.<\/p>\n

But in HD, it seems like these traffic cops are being overwhelmed. The \u201cred light\u201d is no longer functioning properly, and the genes that should stay quiet (the developmental genes) are getting the green light to turn on. This leads to those genes being active when they shouldn\u2019t be, which could cause the neurons<\/a> to behave inappropriately.<\/p>\n

Researchers have discovered that PRC1 isn\u2019t just losing its repressive marks, but the proteins it relies on to work, seem to also be switched out for less mature versions. Think of it like the traffic cops being replaced with rookie officers who aren\u2019t as good at controlling the traffic. This shift could be a major reason why PRC1 is less effective at stopping the activation of developmental genes seen in the mouse model of HD.<\/p>\n

\"Huntington\u2019sHuntington\u2019s disease may cause \u201cgreen lights\u201d for genes that should be off, particularly in certain brain cells that are most vulnerable to the disease. The authors think this could, in part, explain their sensitivity to the disease.<\/p>\n

Image credit: wirestock<\/a><\/p>\n

One of the most interesting findings is that this disruption doesn\u2019t just happen all at once – it gets worse over time. As the HD mice age, more and more genes begin to be activated inappropriately. It\u2019s as if the \u201cgreen lights\u201d keep getting stuck on, while the \u201cred lights\u201d continue to fail. The researchers suggest that this progressive breakdown of genetic traffic regulation may cause the neurons<\/a> to age much faster than they would in a brain without HD. It\u2019s like the cells are \u201caging\u201d more quickly on a genetic level, which might underlie an earlier decline in their function.<\/p>\n

Researchers followed these changes in HD mice and found that over time, the number of genes showing altered epigenetic<\/a> marks kept increasing. In particular, they saw developmental genes becoming more active as the mice aged. Adding to that, they saw this effect specifically in neurons<\/a> in the striatum, the part of the brain most affected in HD.<\/p>\n

In these cells, the epigenetic<\/a> marks that normally keep these genes in check were decreasing, while marks that signal activation were increasing. It\u2019s as if the brakes were failing, and the gas pedal was stuck to the floor – such frantic driving would rapidly age most people!<\/p>\n

\u201c<\/b>A surprising finding from this new work, led by Karine Merienne from the University of Strasbourg in France, is that certain genes that are normally \u201cturned off\u201d are staying \u201con\u201d in the neurons of mice that model HD. <\/p>\n

\u201d<\/p><\/blockquote>\n

Understanding how these epigenetic<\/a> changes contribute to HD opens up exciting possibilities for new treatments in the future. If we can find ways to correct the breakdown in PRC1 and PRC2 function, or restore the balance of the red and green lights at the level of gene regulation, we might be able to slow progression of the disease.<\/p>\n

For example, therapies could aim to fix the loss of repressive marks, which would restore the \u201cred light\u201d and keep developmental genes from turning on inappropriately. Other treatments could target the switch in PRC1 proteins, making sure the \u201cmature\u201d traffic cops are in place, keeping the genes under control.<\/p>\n

Furthermore, therapies that address the accelerated aging of neurons<\/a> could help protect the brain from the damage caused by these epigenetic<\/a> changes. By slowing down the \u201cepigenetic<\/a> aging\u201d process, we might be able to prevent the brain cells from losing their function too quickly.<\/p>\n

The discovery of accelerated epigenetic<\/a> aging in HD gives us a fresh perspective on the disease and offers hope for new treatment strategies. By understanding the role of bivalent promoters, and the malfunctioning PRC1 and PRC2 complexes, researchers could be uncovering how neurons<\/a> in HD may age prematurely and lose their function.<\/p>\n

This new knowledge not only improves our understanding of how HD progresses, but it also opens up the possibility of therapies that could target the underlying epigenetic<\/a> changes. While there is still much to learn, these findings mark an important step forward in the search for ways to pump the brakes on Huntington\u2019s disease.<\/p>\n","protected":false},"excerpt":{"rendered":"By Dr Sarah Hernandez May 15, 2025 Edited by Dr Rachel Harding For Huntington\u2019s disease (HD), a lot…\n","protected":false},"author":2,"featured_media":103440,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[3846],"tags":[267,70,16,15],"class_list":{"0":"post-110671","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-genetics","8":"tag-genetics","9":"tag-science","10":"tag-uk","11":"tag-united-kingdom"},"share_on_mastodon":{"url":"https:\/\/pubeurope.com\/@uk\/114526668949943624","error":""},"_links":{"self":[{"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/posts\/110671","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/comments?post=110671"}],"version-history":[{"count":0,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/posts\/110671\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/media\/103440"}],"wp:attachment":[{"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/media?parent=110671"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/categories?post=110671"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/tags?post=110671"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}