Heparanase Modulates Chromatin Accessibility.
Honglian LiHua ZhangAmelie S WenzZiqi KangHelen WangIsrael VlodavskyXingqi ChenJinping LiPublished in: Cells (2023)
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.
Keyphrases
- genome wide
- wild type
- extracellular matrix
- transcription factor
- single cell
- gene expression
- dna methylation
- dna damage
- high fat diet induced
- cell surface
- rna seq
- copy number
- south africa
- cell therapy
- amino acid
- small molecule
- long non coding rna
- stem cells
- mesenchymal stem cells
- metabolic syndrome
- insulin resistance
- skeletal muscle
- protein protein
- case control