We propose for the first time to divide histone proteolysis into "histone degradation" and the epigenetically connoted "histone clipping". Our initial observation is that these two different classes are very hard to distinguish both experimentally and biologically, because they can both be mediated by the same enzymes. Since the first report decades ago, proteolysis has been found in a broad spectrum of eukaryotic organisms. However, the authors often not clearly distinguish or determine whether degradation or clipping was studied. Given the importance of histone modifications in epigenetic regulation we further elaborate on the different ways in which histone proteolysis could play a role in epigenetics. Finally, unanticipated histone proteolysis has probably left a mark on many studies of histones in the past. In conclusion, we emphasize the significance of reviving the study of histone proteolysis both from a biological and an experimental perspective. Also watch the Video Abstract.
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http://dx.doi.org/10.1002/bies.201400118 | DOI Listing |
Eur J Med Chem
February 2025
Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan Tsuihang New District, Guangdong, 528400, China; Department of Medicinal Chemistry, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China; School of Pharmaceutical Sciences, Southern Medical University, Guangzhou Baiyun District, Guangzhou, Guangdong, 510515, China. Electronic address:
Nuclear receptor binding SET domain protein 2 (NSD2) is involved in various pathologic processes and is considered as an important target for cancer therapy. Due to alternative splicing, NSD2 has 3 isoforms: long, short and RE-IIBP. Although previous studies reported the degradation of PWWP1 domain-containing NSD2-long and short isoforms through PWWP1-binding molecules, the degradation of RE-IIBP which does not contain PWWP1 has been neglected to date.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
December 2024
State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300350, China.
Zygotic genome activation occurs in two-cell (2C) embryos, and a 2C-like state is also activated in sporadic (~1%) naïve embryonic stem cells in mice. Elevated chromatin accessibility is critical for the 2C-like state to occur, yet the underlying molecular mechanisms remain elusive. Zscan4 exhibits burst expression in 2C embryos and 2C-like cells.
View Article and Find Full Text PDFJ Cell Biol
February 2025
Department of Obstetrics and Gynecology, C.S. Mott Center for Human Growth and Development, Wayne State University School of Medicine, Detroit, MI, USA.
Separase regulates multiple aspects of the metaphase-to-anaphase transition. Separase cleaves cohesin to allow chromosome segregation and localizes to vesicles to promote exocytosis. The anaphase-promoting complex/cyclosome (APC/C) activates separase by ubiquitinating its inhibitory chaperone, securin, triggering its degradation.
View Article and Find Full Text PDFBioconjug Chem
December 2024
Division of Chemical Biology and Medicinal Chemistry, College of Pharmacy, The University of Texas at Austin, Austin, Texas 78712, United States.
Histones react with various aldehyde-containing DNA modifications to form reversible but long-lived DNA-histone cross-links. The investigation of their biochemical effects and repair mechanisms has been impeded due to their reversibility and the lack of methods for synthesizing stable and structure-defined DNA-histone cross-links. Herein, we present a visible-light-driven strategy to install an aminooxyhomolysine on a histone at a defined position.
View Article and Find Full Text PDFChem Commun (Camb)
November 2024
Leicester Institute of Structural and Chemical Biology and School of Chemistry, University of Leicester, University Road, Leicester, LE1 7RH, UK.
Histone deacetylase (HDAC) enzymes 1-3 exist in several corepressor complexes and are viable drug targets. To date, proteolysis targeting chimeras (PROTACs) designed to target HDAC1-3 typically exhibit the selective degradation of HDAC3. Herein, we report cereblon-recruiting PROTACs that degrade HDAC1 with selectivity over HDAC3.
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