THRAP3 interacts with and inhibits the transcriptional activity of SOX9 during chondrogenesis

Takashi Sono; Haruhiko Akiyama; Shigenori Miura; Jian Min Deng; Chisa Shukunami; Yuji Hiraki; Yu Tsushima; Yoshiaki Azuma; Richard R. Behringer; Shuichi Matsuda

doi:10.1007/s00774-017-0855-2

THRAP3 interacts with and inhibits the transcriptional activity of SOX9 during chondrogenesis

Takashi Sono, Haruhiko Akiyama, Shigenori Miura, Jian Min Deng, Chisa Shukunami, Yuji Hiraki, Yu Tsushima, Yoshiaki Azuma, Richard R. Behringer, Shuichi Matsuda

Genetics

Research output: Contribution to journal › Article › peer-review

11 Scopus citations

Abstract

Sex-determining region Y (Sry)-box (Sox)9 is required for chondrogenesis as a transcriptional activator of genes related to chondrocyte proliferation, differentiation, and cartilage-specific extracellular matrix. Although there have been studies investigating the Sox9-dependent transcriptional complexes, not all their components have been identified. In the present study, we demonstrated that thyroid hormone receptor-associated protein (THRAP)3 is a component of a SOX9 transcriptional complex by liquid chromatography mass spectrometric analysis of FLAG-tagged Sox9-binding proteins purified from FLAG-HA-tagged Sox9 knock-in mice. Thrap3 knockdown in ATDC5 chondrogenic cells increased the expression of Collagen type II alpha 1 chain (Col2a1) without affecting Sox9 expression. THRAP3 and SOX9 overexpression reduced Col2a1 levels to a greater degree than overexpression of SOX9 alone. The negative regulation of SOX9 transcriptional activity by THRAP3 was mediated by interaction between the proline-, glutamine-, and serine-rich domain of SOX9 and the innominate domain of THRAP3. These results indicate that THRAP3 negatively regulates SOX9 transcriptional activity as a cofactor of a SOX9 transcriptional complex during chondrogenesis.

Original language	English (US)
Pages (from-to)	410-419
Number of pages	10
Journal	Journal of Bone and Mineral Metabolism
Volume	36
Issue number	4
DOIs	https://doi.org/10.1007/s00774-017-0855-2
State	Published - Jul 1 2018

Keywords

Chondrogenesis
Knock-in mouse
LC/MS/MS
SOX9
THRAP3

ASJC Scopus subject areas

Endocrinology, Diabetes and Metabolism
Orthopedics and Sports Medicine
Endocrinology

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10.1007/s00774-017-0855-2

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title = "THRAP3 interacts with and inhibits the transcriptional activity of SOX9 during chondrogenesis",

abstract = "Sex-determining region Y (Sry)-box (Sox)9 is required for chondrogenesis as a transcriptional activator of genes related to chondrocyte proliferation, differentiation, and cartilage-specific extracellular matrix. Although there have been studies investigating the Sox9-dependent transcriptional complexes, not all their components have been identified. In the present study, we demonstrated that thyroid hormone receptor-associated protein (THRAP)3 is a component of a SOX9 transcriptional complex by liquid chromatography mass spectrometric analysis of FLAG-tagged Sox9-binding proteins purified from FLAG-HA-tagged Sox9 knock-in mice. Thrap3 knockdown in ATDC5 chondrogenic cells increased the expression of Collagen type II alpha 1 chain (Col2a1) without affecting Sox9 expression. THRAP3 and SOX9 overexpression reduced Col2a1 levels to a greater degree than overexpression of SOX9 alone. The negative regulation of SOX9 transcriptional activity by THRAP3 was mediated by interaction between the proline-, glutamine-, and serine-rich domain of SOX9 and the innominate domain of THRAP3. These results indicate that THRAP3 negatively regulates SOX9 transcriptional activity as a cofactor of a SOX9 transcriptional complex during chondrogenesis.",

keywords = "Chondrogenesis, Knock-in mouse, LC/MS/MS, SOX9, THRAP3",

author = "Takashi Sono and Haruhiko Akiyama and Shigenori Miura and Deng, {Jian Min} and Chisa Shukunami and Yuji Hiraki and Yu Tsushima and Yoshiaki Azuma and Behringer, {Richard R.} and Shuichi Matsuda",

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AU - Sono, Takashi

AU - Akiyama, Haruhiko

AU - Miura, Shigenori

AU - Deng, Jian Min

AU - Shukunami, Chisa

AU - Hiraki, Yuji

AU - Tsushima, Yu

AU - Azuma, Yoshiaki

AU - Behringer, Richard R.

AU - Matsuda, Shuichi

PY - 2018/7/1

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AB - Sex-determining region Y (Sry)-box (Sox)9 is required for chondrogenesis as a transcriptional activator of genes related to chondrocyte proliferation, differentiation, and cartilage-specific extracellular matrix. Although there have been studies investigating the Sox9-dependent transcriptional complexes, not all their components have been identified. In the present study, we demonstrated that thyroid hormone receptor-associated protein (THRAP)3 is a component of a SOX9 transcriptional complex by liquid chromatography mass spectrometric analysis of FLAG-tagged Sox9-binding proteins purified from FLAG-HA-tagged Sox9 knock-in mice. Thrap3 knockdown in ATDC5 chondrogenic cells increased the expression of Collagen type II alpha 1 chain (Col2a1) without affecting Sox9 expression. THRAP3 and SOX9 overexpression reduced Col2a1 levels to a greater degree than overexpression of SOX9 alone. The negative regulation of SOX9 transcriptional activity by THRAP3 was mediated by interaction between the proline-, glutamine-, and serine-rich domain of SOX9 and the innominate domain of THRAP3. These results indicate that THRAP3 negatively regulates SOX9 transcriptional activity as a cofactor of a SOX9 transcriptional complex during chondrogenesis.

KW - Chondrogenesis

KW - Knock-in mouse

KW - LC/MS/MS

KW - SOX9

KW - THRAP3

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THRAP3 interacts with and inhibits the transcriptional activity of SOX9 during chondrogenesis

Abstract

Keywords

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