biostudies-literatureHojo HNIDDK NIH HHS111315https://www.ebi.ac.uk/biostudies/studies/S-EPMC9510047biostudies-literatureUnknown40(10)The transcriptional regulator Runx2 (runt-related transcription factor 2) has essential but distinct roles in osteoblasts and chondrocytes in skeletal development. However, Runx2-mediated regulatory mechanisms underlying the distinctive programming of osteoblasts and chondrocytes are not well understood. Here, we perform an integrative analysis to investigate Runx2-DNA binding and chromatin accessibility ex vivo using neonatal osteoblasts and chondrocytes. We find that Runx2 engages with cell-type-distinct chromatin-accessible regions, potentially interacting with different combinations of transcriptional regulators, forming cell-type-specific hotspots, and potentiating chromatin accessibility. Genetic analysis and direct cellular reprogramming studies suggest that Runx2 is essential for eCell reportsRunx2 regulates chromatin accessibility to direct the osteoblast program at neonatal stages.PMC9510047P01 DK056246Okada HSaito TKoebis MAiba AAzuma TNakao KGuo QOnodera SChung UITanaka SHe XSuzuki YMcMahon APOhba SHojo HSeki MfalseRunx2 regulates chromatin accessibility to direct the osteoblast program at neonatal stages.The transcriptional regulator Runx2 (runt-related transcription factor 2) has essential but distinct roles in osteoblasts and chondrocytes in skeletal development. However, Runx2-mediated regulatory mechanisms underlying the distinctive programming of osteoblasts and chondrocytes are not well understood. Here, we perform an integrative analysis to investigate Runx2-DNA binding and chromatin accessibility ex vivo using neonatal osteoblasts and chondrocytes. We find that Runx2 engages with cell-type-distinct chromatin-accessible regions, potentially interacting with different combinations of transcriptional regulators, forming cell-type-specific hotspots, and potentiating chromatin accessibility. Genetic analysis and direct cellular reprogramming studies suggest that Runx2 is essential for e2022-01-01T00:00:00Z2022 Sep2026-06-01T02:26:39.808Z2025-04-05T18:20:33.666ZS-EPMC95100473607069110.1016/j.celrep.2022.111315