Uhrf1 is indispensable for normal limb growth by regulating chondrocyte differentiation through specific gene expression [RESEARCH ARTICLE]

Publication Date:
2018-01-09
Publisher:
The Company of Biologists
Print ISSN:
0950-1991
Electronic ISSN:
1477-9129
Topics:
Biology
Keywords:
Chromatin & epigenetics, Musculoskeletal system
Published by:
http://www.biologists.com/
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autor Yamashita, M., Inoue, K., Saeki, N., Ideta-Otsuka, M., Yanagihara, Y., Sawada, Y., Sakakibara, I., Lee, J., Ichikawa, K., Kamei, Y., Iimura, T., Igarashi, K., Takada, Y., Imai, Y.
beschreibung Michiko Yamashita, Kazuki Inoue, Noritaka Saeki, Maky Ideta-Otsuka, Yuta Yanagihara, Yuichiro Sawada, Iori Sakakibara, Jiwon Lee, Koichi Ichikawa, Yoshiaki Kamei, Tadahiro Iimura, Katsuhide Igarashi, Yasutsugu Takada, and Yuuki Imai Transcriptional regulation can be tightly orchestrated by epigenetic regulators. Among these, ubiquitin-like with PHD and RING finger domains 1 (Uhrf1) is reported to have diverse epigenetic functions, including regulation of DNA methylation. However, the physiological functions of Uhrf1 in skeletal tissues remain unclear. Here, we show that limb mesenchymal cell-specific Uhrf1 conditional knockout mice ( Uhrf1 Limb/ Limb ) exhibit remarkably shortened long bones that have morphological deformities due to dysregulated chondrocyte differentiation and proliferation. RNA-seq performed on primary cultured chondrocytes obtained from Uhrf1 Limb/ Limb mice showed abnormal chondrocyte differentiation. In addition, integrative analyses using RNA-seq and MBD-seq revealed that Uhrf1 deficiency decreased genome-wide DNA methylation and increased gene expression through reduced DNA methylation in the promoter regions of 28 genes, including Hspb1 , which is reported to be an IL1-related gene and to affect chondrocyte differentiation. Hspb1 knockdown in cKO chondrocytes can normalize abnormal expression of genes involved in chondrocyte differentiation, such as Mmp13 . These results indicate that Uhrf1 governs cell type-specific transcriptional regulation by controlling the genome-wide DNA methylation status and regulating consequent cell differentiation and skeletal maturation.
citation_standardnr 6133780
datenlieferant ipn_articles
feed_id 1748
feed_publisher The Company of Biologists
feed_publisher_url http://www.biologists.com/
insertion_date 2018-01-09
journaleissn 1477-9129
journalissn 0950-1991
publikationsjahr_anzeige 2018
publikationsjahr_facette 2018
publikationsjahr_intervall 7984:2015-2019
publikationsjahr_sort 2018
publisher The Company of Biologists
quelle Development
relation http://dev.biologists.org/cgi/content/short/145/1/dev157412?rss=1
schlagwort Chromatin & epigenetics, Musculoskeletal system
search_space articles
shingle_author_1 Yamashita, M., Inoue, K., Saeki, N., Ideta-Otsuka, M., Yanagihara, Y., Sawada, Y., Sakakibara, I., Lee, J., Ichikawa, K., Kamei, Y., Iimura, T., Igarashi, K., Takada, Y., Imai, Y.
shingle_author_2 Yamashita, M., Inoue, K., Saeki, N., Ideta-Otsuka, M., Yanagihara, Y., Sawada, Y., Sakakibara, I., Lee, J., Ichikawa, K., Kamei, Y., Iimura, T., Igarashi, K., Takada, Y., Imai, Y.
shingle_author_3 Yamashita, M., Inoue, K., Saeki, N., Ideta-Otsuka, M., Yanagihara, Y., Sawada, Y., Sakakibara, I., Lee, J., Ichikawa, K., Kamei, Y., Iimura, T., Igarashi, K., Takada, Y., Imai, Y.
shingle_author_4 Yamashita, M., Inoue, K., Saeki, N., Ideta-Otsuka, M., Yanagihara, Y., Sawada, Y., Sakakibara, I., Lee, J., Ichikawa, K., Kamei, Y., Iimura, T., Igarashi, K., Takada, Y., Imai, Y.
shingle_catch_all_1 Uhrf1 is indispensable for normal limb growth by regulating chondrocyte differentiation through specific gene expression [RESEARCH ARTICLE]
Chromatin & epigenetics, Musculoskeletal system
Michiko Yamashita, Kazuki Inoue, Noritaka Saeki, Maky Ideta-Otsuka, Yuta Yanagihara, Yuichiro Sawada, Iori Sakakibara, Jiwon Lee, Koichi Ichikawa, Yoshiaki Kamei, Tadahiro Iimura, Katsuhide Igarashi, Yasutsugu Takada, and Yuuki Imai Transcriptional regulation can be tightly orchestrated by epigenetic regulators. Among these, ubiquitin-like with PHD and RING finger domains 1 (Uhrf1) is reported to have diverse epigenetic functions, including regulation of DNA methylation. However, the physiological functions of Uhrf1 in skeletal tissues remain unclear. Here, we show that limb mesenchymal cell-specific Uhrf1 conditional knockout mice ( Uhrf1 Limb/ Limb ) exhibit remarkably shortened long bones that have morphological deformities due to dysregulated chondrocyte differentiation and proliferation. RNA-seq performed on primary cultured chondrocytes obtained from Uhrf1 Limb/ Limb mice showed abnormal chondrocyte differentiation. In addition, integrative analyses using RNA-seq and MBD-seq revealed that Uhrf1 deficiency decreased genome-wide DNA methylation and increased gene expression through reduced DNA methylation in the promoter regions of 28 genes, including Hspb1 , which is reported to be an IL1-related gene and to affect chondrocyte differentiation. Hspb1 knockdown in cKO chondrocytes can normalize abnormal expression of genes involved in chondrocyte differentiation, such as Mmp13 . These results indicate that Uhrf1 governs cell type-specific transcriptional regulation by controlling the genome-wide DNA methylation status and regulating consequent cell differentiation and skeletal maturation.
Yamashita, M., Inoue, K., Saeki, N., Ideta-Otsuka, M., Yanagihara, Y., Sawada, Y., Sakakibara, I., Lee, J., Ichikawa, K., Kamei, Y., Iimura, T., Igarashi, K., Takada, Y., Imai, Y.
The Company of Biologists
0950-1991
09501991
1477-9129
14779129
shingle_catch_all_2 Uhrf1 is indispensable for normal limb growth by regulating chondrocyte differentiation through specific gene expression [RESEARCH ARTICLE]
Chromatin & epigenetics, Musculoskeletal system
Michiko Yamashita, Kazuki Inoue, Noritaka Saeki, Maky Ideta-Otsuka, Yuta Yanagihara, Yuichiro Sawada, Iori Sakakibara, Jiwon Lee, Koichi Ichikawa, Yoshiaki Kamei, Tadahiro Iimura, Katsuhide Igarashi, Yasutsugu Takada, and Yuuki Imai Transcriptional regulation can be tightly orchestrated by epigenetic regulators. Among these, ubiquitin-like with PHD and RING finger domains 1 (Uhrf1) is reported to have diverse epigenetic functions, including regulation of DNA methylation. However, the physiological functions of Uhrf1 in skeletal tissues remain unclear. Here, we show that limb mesenchymal cell-specific Uhrf1 conditional knockout mice ( Uhrf1 Limb/ Limb ) exhibit remarkably shortened long bones that have morphological deformities due to dysregulated chondrocyte differentiation and proliferation. RNA-seq performed on primary cultured chondrocytes obtained from Uhrf1 Limb/ Limb mice showed abnormal chondrocyte differentiation. In addition, integrative analyses using RNA-seq and MBD-seq revealed that Uhrf1 deficiency decreased genome-wide DNA methylation and increased gene expression through reduced DNA methylation in the promoter regions of 28 genes, including Hspb1 , which is reported to be an IL1-related gene and to affect chondrocyte differentiation. Hspb1 knockdown in cKO chondrocytes can normalize abnormal expression of genes involved in chondrocyte differentiation, such as Mmp13 . These results indicate that Uhrf1 governs cell type-specific transcriptional regulation by controlling the genome-wide DNA methylation status and regulating consequent cell differentiation and skeletal maturation.
Yamashita, M., Inoue, K., Saeki, N., Ideta-Otsuka, M., Yanagihara, Y., Sawada, Y., Sakakibara, I., Lee, J., Ichikawa, K., Kamei, Y., Iimura, T., Igarashi, K., Takada, Y., Imai, Y.
The Company of Biologists
0950-1991
09501991
1477-9129
14779129
shingle_catch_all_3 Uhrf1 is indispensable for normal limb growth by regulating chondrocyte differentiation through specific gene expression [RESEARCH ARTICLE]
Chromatin & epigenetics, Musculoskeletal system
Michiko Yamashita, Kazuki Inoue, Noritaka Saeki, Maky Ideta-Otsuka, Yuta Yanagihara, Yuichiro Sawada, Iori Sakakibara, Jiwon Lee, Koichi Ichikawa, Yoshiaki Kamei, Tadahiro Iimura, Katsuhide Igarashi, Yasutsugu Takada, and Yuuki Imai Transcriptional regulation can be tightly orchestrated by epigenetic regulators. Among these, ubiquitin-like with PHD and RING finger domains 1 (Uhrf1) is reported to have diverse epigenetic functions, including regulation of DNA methylation. However, the physiological functions of Uhrf1 in skeletal tissues remain unclear. Here, we show that limb mesenchymal cell-specific Uhrf1 conditional knockout mice ( Uhrf1 Limb/ Limb ) exhibit remarkably shortened long bones that have morphological deformities due to dysregulated chondrocyte differentiation and proliferation. RNA-seq performed on primary cultured chondrocytes obtained from Uhrf1 Limb/ Limb mice showed abnormal chondrocyte differentiation. In addition, integrative analyses using RNA-seq and MBD-seq revealed that Uhrf1 deficiency decreased genome-wide DNA methylation and increased gene expression through reduced DNA methylation in the promoter regions of 28 genes, including Hspb1 , which is reported to be an IL1-related gene and to affect chondrocyte differentiation. Hspb1 knockdown in cKO chondrocytes can normalize abnormal expression of genes involved in chondrocyte differentiation, such as Mmp13 . These results indicate that Uhrf1 governs cell type-specific transcriptional regulation by controlling the genome-wide DNA methylation status and regulating consequent cell differentiation and skeletal maturation.
Yamashita, M., Inoue, K., Saeki, N., Ideta-Otsuka, M., Yanagihara, Y., Sawada, Y., Sakakibara, I., Lee, J., Ichikawa, K., Kamei, Y., Iimura, T., Igarashi, K., Takada, Y., Imai, Y.
The Company of Biologists
0950-1991
09501991
1477-9129
14779129
shingle_catch_all_4 Uhrf1 is indispensable for normal limb growth by regulating chondrocyte differentiation through specific gene expression [RESEARCH ARTICLE]
Chromatin & epigenetics, Musculoskeletal system
Michiko Yamashita, Kazuki Inoue, Noritaka Saeki, Maky Ideta-Otsuka, Yuta Yanagihara, Yuichiro Sawada, Iori Sakakibara, Jiwon Lee, Koichi Ichikawa, Yoshiaki Kamei, Tadahiro Iimura, Katsuhide Igarashi, Yasutsugu Takada, and Yuuki Imai Transcriptional regulation can be tightly orchestrated by epigenetic regulators. Among these, ubiquitin-like with PHD and RING finger domains 1 (Uhrf1) is reported to have diverse epigenetic functions, including regulation of DNA methylation. However, the physiological functions of Uhrf1 in skeletal tissues remain unclear. Here, we show that limb mesenchymal cell-specific Uhrf1 conditional knockout mice ( Uhrf1 Limb/ Limb ) exhibit remarkably shortened long bones that have morphological deformities due to dysregulated chondrocyte differentiation and proliferation. RNA-seq performed on primary cultured chondrocytes obtained from Uhrf1 Limb/ Limb mice showed abnormal chondrocyte differentiation. In addition, integrative analyses using RNA-seq and MBD-seq revealed that Uhrf1 deficiency decreased genome-wide DNA methylation and increased gene expression through reduced DNA methylation in the promoter regions of 28 genes, including Hspb1 , which is reported to be an IL1-related gene and to affect chondrocyte differentiation. Hspb1 knockdown in cKO chondrocytes can normalize abnormal expression of genes involved in chondrocyte differentiation, such as Mmp13 . These results indicate that Uhrf1 governs cell type-specific transcriptional regulation by controlling the genome-wide DNA methylation status and regulating consequent cell differentiation and skeletal maturation.
Yamashita, M., Inoue, K., Saeki, N., Ideta-Otsuka, M., Yanagihara, Y., Sawada, Y., Sakakibara, I., Lee, J., Ichikawa, K., Kamei, Y., Iimura, T., Igarashi, K., Takada, Y., Imai, Y.
The Company of Biologists
0950-1991
09501991
1477-9129
14779129
shingle_title_1 Uhrf1 is indispensable for normal limb growth by regulating chondrocyte differentiation through specific gene expression [RESEARCH ARTICLE]
shingle_title_2 Uhrf1 is indispensable for normal limb growth by regulating chondrocyte differentiation through specific gene expression [RESEARCH ARTICLE]
shingle_title_3 Uhrf1 is indispensable for normal limb growth by regulating chondrocyte differentiation through specific gene expression [RESEARCH ARTICLE]
shingle_title_4 Uhrf1 is indispensable for normal limb growth by regulating chondrocyte differentiation through specific gene expression [RESEARCH ARTICLE]
timestamp 2025-06-30T23:31:53.183Z
titel Uhrf1 is indispensable for normal limb growth by regulating chondrocyte differentiation through specific gene expression [RESEARCH ARTICLE]
titel_suche Uhrf1 is indispensable for normal limb growth by regulating chondrocyte differentiation through specific gene expression [RESEARCH ARTICLE]
topic W
uid ipn_articles_6133780