PHF20 positively regulates osteoblast differentiation via increasing the expression and activation of Runx2 with enrichment of H3K4me3

Abstract Plant homeodomain finger protein 20 (PHF20), a methyl lysine effector protein, is a component MOF-NSL lysine acetyltranferase complex. Global deletion of PHF20 has shown spinal bone defects and reduced skeletal formation. However, the molecular basis of PHF20 involved in skeletal developmen...

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Autores principales: Jin-Woo Yang, Byung-Chul Jeong, Jongsun Park, Jeong-Tae Koh
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Publicado: Nature Portfolio 2017
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Acceso en línea:https://doaj.org/article/e1b9d9b92f36461d97e562c8e8233735
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spelling oai:doaj.org-article:e1b9d9b92f36461d97e562c8e82337352021-12-02T12:32:20ZPHF20 positively regulates osteoblast differentiation via increasing the expression and activation of Runx2 with enrichment of H3K4me310.1038/s41598-017-08868-02045-2322https://doaj.org/article/e1b9d9b92f36461d97e562c8e82337352017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08868-0https://doaj.org/toc/2045-2322Abstract Plant homeodomain finger protein 20 (PHF20), a methyl lysine effector protein, is a component MOF-NSL lysine acetyltranferase complex. Global deletion of PHF20 has shown spinal bone defects and reduced skeletal formation. However, the molecular basis of PHF20 involved in skeletal development has not been elucidated yet. The objective of this study was to determine the role of PHF20 in osteoblast differentiation and mineralization. Expression of PHF20 was gradually increased during osteoblast differentiation. Overexpression of PHF20 enhanced ALP activity and mineralized nodule formation as well as the expression of osteogenic markers including Runx2. In contrast, inhibition of PHF20 expression reduced osteoblast differentiation and mineralization. Mechanistically, PHF20 increased the promoter activity of osteogenic genes including Og2, Alp, and Bsp through direct association with Runx2. Moreover, PHF20 increased the enrichment of H3K4me3 on the promoter of Runx2 followed by increased Runx2 promoter activity. Interestingly, Bix-01294, a histone methylation inhibitor, decreased mineralized nodule formation through decreasing the levels of H3K4me3 and Runx2. Overexpression of PHF20 restored the Bix-01294 effects. Taken together, these results indicate that methyl lysine-binding protein PHF20 might be a novel regulator of osteoblast differentiation.Jin-Woo YangByung-Chul JeongJongsun ParkJeong-Tae KohNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Jin-Woo Yang
Byung-Chul Jeong
Jongsun Park
Jeong-Tae Koh
PHF20 positively regulates osteoblast differentiation via increasing the expression and activation of Runx2 with enrichment of H3K4me3
description Abstract Plant homeodomain finger protein 20 (PHF20), a methyl lysine effector protein, is a component MOF-NSL lysine acetyltranferase complex. Global deletion of PHF20 has shown spinal bone defects and reduced skeletal formation. However, the molecular basis of PHF20 involved in skeletal development has not been elucidated yet. The objective of this study was to determine the role of PHF20 in osteoblast differentiation and mineralization. Expression of PHF20 was gradually increased during osteoblast differentiation. Overexpression of PHF20 enhanced ALP activity and mineralized nodule formation as well as the expression of osteogenic markers including Runx2. In contrast, inhibition of PHF20 expression reduced osteoblast differentiation and mineralization. Mechanistically, PHF20 increased the promoter activity of osteogenic genes including Og2, Alp, and Bsp through direct association with Runx2. Moreover, PHF20 increased the enrichment of H3K4me3 on the promoter of Runx2 followed by increased Runx2 promoter activity. Interestingly, Bix-01294, a histone methylation inhibitor, decreased mineralized nodule formation through decreasing the levels of H3K4me3 and Runx2. Overexpression of PHF20 restored the Bix-01294 effects. Taken together, these results indicate that methyl lysine-binding protein PHF20 might be a novel regulator of osteoblast differentiation.
format article
author Jin-Woo Yang
Byung-Chul Jeong
Jongsun Park
Jeong-Tae Koh
author_facet Jin-Woo Yang
Byung-Chul Jeong
Jongsun Park
Jeong-Tae Koh
author_sort Jin-Woo Yang
title PHF20 positively regulates osteoblast differentiation via increasing the expression and activation of Runx2 with enrichment of H3K4me3
title_short PHF20 positively regulates osteoblast differentiation via increasing the expression and activation of Runx2 with enrichment of H3K4me3
title_full PHF20 positively regulates osteoblast differentiation via increasing the expression and activation of Runx2 with enrichment of H3K4me3
title_fullStr PHF20 positively regulates osteoblast differentiation via increasing the expression and activation of Runx2 with enrichment of H3K4me3
title_full_unstemmed PHF20 positively regulates osteoblast differentiation via increasing the expression and activation of Runx2 with enrichment of H3K4me3
title_sort phf20 positively regulates osteoblast differentiation via increasing the expression and activation of runx2 with enrichment of h3k4me3
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/e1b9d9b92f36461d97e562c8e8233735
work_keys_str_mv AT jinwooyang phf20positivelyregulatesosteoblastdifferentiationviaincreasingtheexpressionandactivationofrunx2withenrichmentofh3k4me3
AT byungchuljeong phf20positivelyregulatesosteoblastdifferentiationviaincreasingtheexpressionandactivationofrunx2withenrichmentofh3k4me3
AT jongsunpark phf20positivelyregulatesosteoblastdifferentiationviaincreasingtheexpressionandactivationofrunx2withenrichmentofh3k4me3
AT jeongtaekoh phf20positivelyregulatesosteoblastdifferentiationviaincreasingtheexpressionandactivationofrunx2withenrichmentofh3k4me3
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