Heparanase Modulates Chromatin Accessibility

Author:

Li Honglian1ORCID,Zhang Hua2,Wenz Amelie2ORCID,Kang Ziqi2,Wang Helen1,Vlodavsky Israel3,Chen Xingqi2ORCID,Li Jinping1

Affiliation:

1. SciLifeLab Uppsala, The Biomedical Center, Department of Medical Biochemistry and Microbiology, University of Uppsala, 75237 Uppsala, Sweden

2. Department of Immunology, Genetic and Pathology, University of Uppsala, 75237 Uppsala, Sweden

3. Technion Integrated Cancer Center (TICC), Rappaport, Faculty of Medicine, Technion, Haifa 31096, Israel

Abstract

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.

Funder

Swedish Research Council

Swedish Cancer Foundation

Publisher

MDPI AG

Subject

General Medicine

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