Demethylation of SFRP2 by histone demethylase KDM2A regulated osteo‐/dentinogenic differentiation of stem cells of the apical papilla

Abstract

Our results have identified a new function of SFRP2 and shed new light on the molecular mechanism underlying directed differentiation of stem cells of dental origin.

A demethylation deficient isoform of the lysine demethylase KDM2A interacts with pericentromeric heterochromatin in an HP1a-dependent manner

“…2,[6][7][8] Although H3K36me3 and H3K36me2 are associated mainly with active gene bodies, where they prevent spurious transcription initiations, H3K36me2 has been also found to be associated with transcriptionally active gene promoters and its removal by KDM2A leads to transcriptional repression of such promoters. 1,[9][10][11][12][13][14][15][16][17][18][19] The short demethylation-defiecient KDM2A isoform KDM2A-SF lacks the N-terminal demethylation domain, but it retains the ability to bind to CpG islands. 15,23,24 KDM2A-SF is therefore likely to compete with KDM2A-LF for the same CpG islands.…”

“…2,[6][7][8] Although methylation of H3K36 is known to repress spurious transcription initiation in bodies of transcriptionally active genes and it has been detected on promoters of transcriptionally repressed genes, H3K36me2 has been also shown to be associated with transcriptionally active promoters. 2,[9][10][11][12][13][14][15] Demethylation of promoter-associated H3K36me2 by KDM2A has been shown to result in transcriptional repression of these promoters, whereas a loss of KDM2A leads to increased levels of promoter-associated H3K36me2 and transcriptional de-repression of these promoters. 10,14,[16][17][18][19] KDM2A also demethylates lysine residues of non-histone proteins such as the NF-kB p65 subunit or b-catenin.…”

“…2,[9][10][11][12][13][14][15] Demethylation of promoter-associated H3K36me2 by KDM2A has been shown to result in transcriptional repression of these promoters, whereas a loss of KDM2A leads to increased levels of promoter-associated H3K36me2 and transcriptional de-repression of these promoters. 10,14,[16][17][18][19] KDM2A also demethylates lysine residues of non-histone proteins such as the NF-kB p65 subunit or b-catenin. 20,21 KDM2A has been found to be misregulated in various cancers and its loss-of-function mouse mutants are embryonically lethal.…”

KDM1A regulated the osteo/dentinogenic differentiation process of the stem cells of the apical papilla via binding with PLOD2

“…First, the teeth were stored under sterile conditions and rinsed with phosphate‐buffered saline (PBS). The tissue of the apical papilla was cut from the immature apical tissue, and the SCAPs were cultured according to previous methods . Subsequently, the separated tissues were placed in a solution of 4 mg/mL of dispase (Roche Diagnostics Corp., Indianapolis, IN, USA) and 3 mg/mL of collagenase type I (Worthington Biochemical Corp., Lakewood, NJ, USA) for 1 h at 37°C.…”

“…The tissue of the apical papilla was cut from the immature apical tissue, and the SCAPs were cultured according to previous methods. 18,19 Subsequently, the separated tissues were placed in a solution of 4 mg/mL of dispase (Roche Diagnostics Corp., Indianapolis, IN, USA) and 3 mg/mL of collagenase type I (Worthington Biochemical Corp., Lakewood, NJ, USA) for 1 h at 37°C. The single-cell suspensions were filtered using a 70μm strainer (Falcon, BD Lab ware, Franklin Lakes, NJ, USA).…”