Over the past few years, the ?epigenetic? regulation of the genome has become increasingly important to understanding both the etiology and fundamental mechanisms of aging and age-related diseases. Key to epigenetic regulation are two classes of lysine-modifying enzymes, the histone deacetylases (sirtuins and HDACs) and the histone acetyltransferases (HATs), also known as erasers and writers, respectively. Acetyl-lysine neutralizes the cationic charge relative to the naked Lys sidechain and also creates an attractive surface for binding to proteins containing bromodomains, also known as reader proteins. These acetyl-Lys writers, erasers, and readers are critical for maintaining normal expression patterns, cell cycle progression, DNA repair, stem cells, mitochondria, cell fate, and differentiation. Alterations in the functions of these acetyl-Lys related proteins have been linked to epigenetic silencing of gene expression including tumor suppressor genes, leading to cancer cell proliferation. Moreover, changes in acetyl-Lys pathways are believed to contribute to a variety of other diseases and aging mechanisms. Several broad spectrum HDAC inhibitors have been approved by FDA to treat various cancers. Their precise molecular mechanisms in controlling cancer and influencing other biomedical processes remain elusive. Although targeting HATs for therapeutic purposes has been relatively slow compared to targeting deacetylases, exciting new progress has also been made in recent years, including the recent discovery of A- 485 as a p300/CBP inhibitor. In addition, targeting bromodomains in cancer is a very active area. As the only conference dedicated to protein acetylation, this biannual meeting plays an essential role in bringing together more than 40 world leaders and ~120 participants. A primary objective is to transfer knowledge and foster collaboration between basic academic researchers, clinical scientists, and industrial researchers to understand how lysine acetylation controls human health and how to prevent and treat a diverse set of cancers and age-related diseases. A second objective is to foster the development and interests of younger investigators to help support their career development. The participants stay and eat at the meeting venue so they have ample time to for informal brainstorming and networking. There are 16 planned talks from junior scientists selected from the submitted abstracts, which is important for their career development. We will also have a panel discussion on professional development and career options, aimed to provide further support for the young investigators. Moreover, there will be a series of ask the experts discussion sections over lunch that will allow attendees to gain insight into specialized technologies (mass spectrometry, structural approaches, chemical biology methods, imaging strategies) that will be highlighted at the meeting. This meeting is particularly timely because of a linkage of acetylation, metabolism, and cancer. Furthermore, exciting new fundamental discoveries are continuing to be reported, such as the discovery of new lysine post-translational modifications (e.g. 3-hydroxybutyryl lysine and palmitoyl lysine) that can be removed by sirtuins or HDACs, and the discovery that these modifications can regulate transcription, cell signaling, and protein secretion. Therefore, support is requested for the 7th biannual FASEB conference on reversible protein acetylation in health and disease to be held in Lisbon, Portugal August 4 -9, 2019.
Significance Increasing evidence points to the dysregulation of the epigenome, and the resulting changes in gene expression and nuclear architecture, as a key driver of cancer and age-related diseases, a process that may be reversible. Central to controlling the epigenome are lysine-modifying enzymes known are the histone acetyltransferases, (HATs) and the histone deacetylases (sirtuins and HDACs) and the bromodomain acetyl- Lys binding proteins. These proteins play known roles in cancer, metabolic diseases, and aging. New therapeutic approaches, dietary interventions, and chemoprevention studies are under active investigation and will be featured at this meeting. This conference will bring together experts doing basic research to understand how these enzymes function with clinical experts testing new agents with leaders from industry who are developing innovative strategies to treat diseases and improve human health worldwide.
