Heparanase Modulates Chromatin Accessibility

• Published in: Cells (Basel, Switzerland) Vol. 12; no. 6; p. 891
• Main Authors: Li, Honglian, Zhang, Hua, Wenz, Amelie, Kang, Ziqi, Wang, Helen, Vlodavsky, Israel, Chen, Xingqi, Li, Jinping
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.03.2023; MDPI
• Subjects: Analysis; Angiogenesis; Animals; ATAC-seq; Bioavailability; Cancer; Cancer therapies; Care and treatment; Cell surface; Chromatin; Cytokines; Diagnosis; DNA sequencing; Embryo fibroblasts; Enzymes; epigenetics; Extracellular matrix; Fibroblasts; Fibroblasts - metabolism; Gene expression; Genetic aspects; Genomes; Glucuronidase - metabolism; Growth factors; Health aspects; Heparan sulfate; heparanase; Heparitin Sulfate - metabolism; histone; Histone H3; Histones; Inflammation; Localization; Medical prognosis; Metastasis; Mice; Monoclonal antibodies; Multiple myeloma; Nucleotide sequencing; Signal transduction; Sulfates; Transposase; Tumorigenesis; Sweden; heparanase; histone; ATAC-seq; epigenetics
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells12060891

Heparanase is the sole endoglucuronidase that degrades heparan sulfate in the cell surface and extracellular matrix (ECM). Several studies have reported the localization of heparanase in the cell nucleus, but the functional role of the nuclear enzyme is still obscure. Subjecting mouse embryonic fibroblasts (MEFs) derived from heparanase knockout (Hpse-KO) mice and applying transposase-accessible chromatin with sequencing (ATAC-seq), we revealed that heparanase is involved in the regulation of chromatin accessibility. Integrating with genome-wide analysis of chromatin states revealed an overall low activity in the enhancer and promoter regions of Hpse-KO MEFs compared with wild-type (WT) MEFs. Western blot analysis of MEFs and tissues derived from Hpse-KO vs. WT mice confirmed reduced expression of H3K27ac (acetylated lysine at N-terminal position 27 of the histone H3 protein). Our results offer a mechanistic explanation for the well-documented attenuation of inflammatory responses and tumor growth in Hpse-KO mice.