During normal development, histone modifications control the fate of cells, whereas histone modification affects the process of cell dedifferentiation in the event of disease. In a recent study published in the international journals JCI, researchers from Canada decided to find out how dynamic changes in histone modifications can affect adult glomerular podocytes, which are usually at rest.
To do this, the researchers altered the inhibitory effect of H3K27me3 in podocytes and performed a series of analyzes. Adriamycin nephrotoxicity test and subtotal nephrectomy both showed that the level of H3K27me3 decreased after the removal of methyltransferase EZH2 with histone methylation in podocytes and the mice were susceptible to glomerular diseases. The researchers found that in podocytes H3K27me3 aggregates in the promoter region of Notch ligand Jag1, and inhibition of Jag1 by EZH2 knockdown or knockdown of EZH2 expression can promote podocyte dedifferentiation. In contrast, inhibition of the demethylase Jmjd3 and UTX increased the level of H3K27me3, decreased adriamycin nephrotoxicity experiments, subtotal nephrectomy, and diabetic-induced glomerular disease. In addition, the researchers analyzed glomerular podocytes in patients with focal segmental glomerulosclerosis and diabetic nephropathy and found that glomerular podocytes in these patients exhibited levels of H3K27me3 Decline and UTX levels increase. Similar to this observation, inhibition of Jmjd3 and UTX slows the progression of nephropathy in a mouse model of glomerular damage.
Collectively, these results indicate that chromatin modifications are not as stable as they appear to be at rest, and also undergo dynamic regulation, whereas epigenetic reprogramming or results that may improve glomerular disease.
Collected by Creative BioMart.
