{"id":61233,"date":"2023-07-21T09:15:00","date_gmt":"2023-07-21T07:15:00","guid":{"rendered":"https:\/\/www.embl.org\/news\/?p=61233"},"modified":"2024-07-23T14:39:29","modified_gmt":"2024-07-23T12:39:29","slug":"a-glimpse-into-the-hexasome-40-years-on","status":"publish","type":"post","link":"https:\/\/www.embl.org\/news\/science\/a-glimpse-into-the-hexasome-40-years-on\/","title":{"rendered":"A glimpse into the hexasome: 40 years on"},"content":{"rendered":"\n

In 1983, scientists discovered hexasomes \u2013 a unique molecular structure that helps cells package their DNA. Now, a study conducted by the Eustermann group<\/a> at EMBL Heidelberg has shed light on how DNA packaging into hexasomes can affect the function of enzymes involved in gene regulation.<\/p>\n\n\n\n

DNA: a lot to unpack<\/strong><\/h2>\n\n\n\n

DNA is a very long, thin thread containing our genetic instructions. Being much longer than the tiny space inside our cells, it needs a clever packaging system. That\u2019s where nucleosomes come into play \u2013 tiny spool-like structures that help compact our genetic information. Multiple nucleosomes are then linked together in a ‘beads-on-a-string’ arrangement, collectively making up chromatin \u2013 a compact fiber comprising genetic material (DNA) and the proteins that help package and organise it (e.g. histones). <\/p>\n\n\n\n

Nucleosomes also play a crucial role in regulating gene activity, determining which genes are switched on or off. The Eustermann group at EMBL Heidelberg aims to understand how these structures work in the context of DNA packaging.<\/p>\n\n\n\n

\u201cWe are interested in understanding the molecular principles by which DNA is packaged in the nucleus of a eukaryotic cell,\u201d said Sebastian Eustermann, Group Leader at EMBL Heidelberg. \u201cOur focus lies specifically on visualising the molecular processes of how this packaging then regulates the expression and maintenance of the genome.\u201d<\/p>\n\n\n\n

Nucleosomes and hexasomes under the cryo-EM lens<\/strong><\/h2>\n\n\n\n

Nucleosomes can exist in different structural versions, known as non-canonical forms, which may play a fundamental, yet so far largely unexplored, role in genome regulation. The hexasome is one such version. A standard nucleosome wraps DNA around eight histone proteins, while a hexasome uses only six. Such small structural differences can play a major role in the molecular realm of the cell.<\/p>\n\n\n\n

In recent years, thanks to breakthroughs in cryo-electron microscopy (cryo-EM), researchers were finally able to solve the structure of canonical nucleosomes along with their interacting proteins, providing unprecedented insights into how they collectively regulate the genome. However, until now, the molecular details of hexasomes and their interactors remained unclear \u2013 a gap Eustermann\u2019s team has been trying to fill.<\/p>\n\n\n\n

\u201cForty years ago, hexasomes were discovered by my PhD mentor Daniela Rhodes. Now, my team could finally obtain first insights into how hexasomes impact the function of enzymes called chromatin remodelers,\u201d said Eustermann. <\/p>\n\n\n\n

Chromatin remodelling enzymes are crucial for maintaining the dynamic nature of chromatin packaging. Their activity can change chromatin structure and accessibility, leading to alterations in gene expression patterns. <\/p>\n\n\n\n

\u201cThese enzymes work like molecular machines. Fuelled by ATP, an energy-rich cellular compound, they can spool DNA around histones,\u201d explained Anna Jungblut, co-author of the study and PhD student in the Eustermann group. <\/em>\u201cRemodelers play a vital role in regulating the genome and have significant effects on cell function. For example, when gene regulation is disrupted, it frequently contributes to diseases like cancer.\u201d <\/p>\n\n\n\n

To investigate this process, the team made extensive use of cryo-EM, which allowed them to look at the atomic structure of a hexasome bound to a chromatin remodeler. They found that remodelers recognise and modify the structure of hexasomes, indicating that these non-canonical nucleosomes not only affect the way DNA is packaged, but also impact how enzymes interpret the regulatory information within chromatin.<\/p>\n\n\n\n

\u201cOur study uncovers how certain features of hexasomes can activate and regulate chromatin remodelling enzymes. These intriguing insights may inspire studies on other molecular machines in the nucleus of a cell,\u201d said Min Zhang, first author of the study and EIPOD postdoc in the Eustermann group. \u201cHexasomes are likely to have a similar impact on human remodelling enzymes closely linked to cancer. Follow-up studies on the regulation of hexasomes on the genome would provide new perspectives in gene regulation.\u201d<\/p>\n\n\n\n

The discovery is further bolstered by findings<\/a> from Yifan Cheng\u2019s and Geeta Narlikar\u2019s research groups at UCSF, who have shown structurally that chromatin remodelling enzymes become activated on hexasomes, even though hexasomes lack features that were previously thought to be essential for the enzymes to function. In an earlier study<\/a>, the Narlikar group had demonstrated biochemically the link between hexasomes and chromatin remodelling.<\/p>\n\n\n\n

\u201cWhen Geeta Narlikar and I met at a conference last year, we were astonished that we independently made the discovery of how remodelers achieve their function on hexasomes,\u201d said Eustermann. \u201cAgain an example of how we can benefit from open exchanges and collaborative discussions in science.\u201d<\/p>\n","protected":false},"excerpt":{"rendered":"

Research from the Eustermann group at EMBL Heidelberg reveals how the packaging of DNA into hexasomes impacts the function of enzymes involved in gene regulation.<\/p>\n","protected":false},"author":159,"featured_media":61327,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[2,17591],"tags":[718,17251,13658,43,17247,79,17693,17249,35],"embl_taxonomy":[9796,19249],"class_list":["post-61233","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-science","category-science-technology","tag-cryo-em","tag-epigenetic","tag-eustermann","tag-heidelberg","tag-hexasome","tag-microscopy","tag-molecular-systems-biology","tag-nucleosome","tag-structural-biology","embl_taxonomy-embl-heidelberg","embl_taxonomy-eustermann-group"],"acf":{"featured":true,"show_featured_image":false,"field_target_display":"embl","field_article_language":{"value":"english","label":"English"},"article_intro":"

Research from the Eustermann group at EMBL Heidelberg reveals how the packaging of DNA into hexasomes impacts the function of enzymes involved in gene regulation<\/p>\n","related_links":[{"link_description":"Eustermann Group","link_url":"https:\/\/www.embl.org\/groups\/eustermann\/"},{"link_description":"EMBL Heidelberg","link_url":"https:\/\/www.embl.org\/sites\/heidelberg\/"},{"link_description":"Narlikar Group (UCSF)","link_url":"https:\/\/narlikarlab.ucsf.edu\/"}],"source_article":[{"publication_title":"Hexasome-INO80 complex reveals structural basis of noncanonical nucleosome remodeling","publication_link":{"title":"","url":"https:\/\/www.science.org\/doi\/10.1126\/science.adf6287","target":""},"publication_authors":"Zhang M., et al.","publication_source":"Science ","publication_date":"29 June 2023","publication_doi":"DOI: 10.1126\/science.adf6287"}],"in_this_article":false,"press_contact":"None","article_translations":false,"languages":"","vf_locked":false},"embl_taxonomy_terms":[{"uuid":"a:3:{i:0;s:36:\"b14d3f13-5670-44fb-8970-e54dfd9c921a\";i:1;s:36:\"89e00fee-87f4-482e-a801-4c3548bb6a58\";i:2;s:36:\"ab46b6d4-71d8-49f8-b2f4-b326d4c8ea4e\";}","parents":[],"name":["EMBL Heidelberg"],"slug":"embl-heidelberg","description":"Where > All EMBL sites > EMBL Heidelberg"},{"uuid":"a:3:{i:0;s:36:\"302cfdf7-365b-462a-be65-82c7b783ebf7\";i:1;s:36:\"bd910dd7-0cda-4618-8bfa-d37fbda8438e\";i:2;s:36:\"c56bf10e-2862-486e-a484-8560bb6bb279\";}","parents":[],"name":["Eustermann Group"],"slug":"eustermann-group","description":"What > Molecular Systems Biology > Eustermann Group"}],"yoast_head":"\nA glimpse into the hexasome: 40 years on | EMBL<\/title>\n<meta name=\"description\" content=\"Researchers at EMBL Heidelberg reveal how the packaging of DNA into hexasomes impacts the function of enzymes involved in gene 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