Meis Cofactors Control HDAC and CBP Accessibility at Hox-Regulated Promoters during Zebrafish Embryogenesis

Seong Kyu Choe, Peiyuan Lu, Mako Nakamura, Jinhyup Lee, Charles G. Sagerström

研究成果: ジャーナルへの寄稿記事

55 引用 (Scopus)

抄録

Hox proteins form complexes with Pbx and Meis cofactors to control gene expression, but the role of Meis is unclear. We demonstrate that Hoxb1-regulated promoters are highly acetylated on histone H4 (AcH4) and occupied by Hoxb1, Pbx, and Meis in zebrafish tissues where these promoters are active. Inhibition of Meis blocks gene expression and reduces AcH4 levels at these promoters, suggesting a role for Meis in maintaining AcH4. Within Hox transcription complexes, Meis binds directly to Pbx and we find that this binding displaces histone deacetylases (HDACs) from Hoxb1-regulated promoters in zebrafish embryos. Accordingly, Pbx mutants that cannot bind Meis act as repressors by recruiting HDACs and reducing AcH4 levels, while Pbx mutants that bind neither HDAC nor Meis are constitutively active and recruit CBP to increase AcH4 levels. We conclude that Meis acts, at least in part, by controlling access of HDAC and CBP to Hox-regulated promoters.

元の言語英語
ページ(範囲)561-567
ページ数7
ジャーナルDevelopmental Cell
17
発行部数4
DOI
出版物ステータス出版済み - 10 20 2009
外部発表Yes

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Histone Deacetylases
Zebrafish
Embryonic Development
Gene expression
Gene Expression
Transcription
Histones
Embryonic Structures
Tissue
Proteins

All Science Journal Classification (ASJC) codes

  • Developmental Biology

これを引用

Meis Cofactors Control HDAC and CBP Accessibility at Hox-Regulated Promoters during Zebrafish Embryogenesis. / Choe, Seong Kyu; Lu, Peiyuan; Nakamura, Mako; Lee, Jinhyup; Sagerström, Charles G.

:: Developmental Cell, 巻 17, 番号 4, 20.10.2009, p. 561-567.

研究成果: ジャーナルへの寄稿記事

Choe, Seong Kyu ; Lu, Peiyuan ; Nakamura, Mako ; Lee, Jinhyup ; Sagerström, Charles G. / Meis Cofactors Control HDAC and CBP Accessibility at Hox-Regulated Promoters during Zebrafish Embryogenesis. :: Developmental Cell. 2009 ; 巻 17, 番号 4. pp. 561-567.
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abstract = "Hox proteins form complexes with Pbx and Meis cofactors to control gene expression, but the role of Meis is unclear. We demonstrate that Hoxb1-regulated promoters are highly acetylated on histone H4 (AcH4) and occupied by Hoxb1, Pbx, and Meis in zebrafish tissues where these promoters are active. Inhibition of Meis blocks gene expression and reduces AcH4 levels at these promoters, suggesting a role for Meis in maintaining AcH4. Within Hox transcription complexes, Meis binds directly to Pbx and we find that this binding displaces histone deacetylases (HDACs) from Hoxb1-regulated promoters in zebrafish embryos. Accordingly, Pbx mutants that cannot bind Meis act as repressors by recruiting HDACs and reducing AcH4 levels, while Pbx mutants that bind neither HDAC nor Meis are constitutively active and recruit CBP to increase AcH4 levels. We conclude that Meis acts, at least in part, by controlling access of HDAC and CBP to Hox-regulated promoters.",
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T1 - Meis Cofactors Control HDAC and CBP Accessibility at Hox-Regulated Promoters during Zebrafish Embryogenesis

AU - Choe, Seong Kyu

AU - Lu, Peiyuan

AU - Nakamura, Mako

AU - Lee, Jinhyup

AU - Sagerström, Charles G.

PY - 2009/10/20

Y1 - 2009/10/20

N2 - Hox proteins form complexes with Pbx and Meis cofactors to control gene expression, but the role of Meis is unclear. We demonstrate that Hoxb1-regulated promoters are highly acetylated on histone H4 (AcH4) and occupied by Hoxb1, Pbx, and Meis in zebrafish tissues where these promoters are active. Inhibition of Meis blocks gene expression and reduces AcH4 levels at these promoters, suggesting a role for Meis in maintaining AcH4. Within Hox transcription complexes, Meis binds directly to Pbx and we find that this binding displaces histone deacetylases (HDACs) from Hoxb1-regulated promoters in zebrafish embryos. Accordingly, Pbx mutants that cannot bind Meis act as repressors by recruiting HDACs and reducing AcH4 levels, while Pbx mutants that bind neither HDAC nor Meis are constitutively active and recruit CBP to increase AcH4 levels. We conclude that Meis acts, at least in part, by controlling access of HDAC and CBP to Hox-regulated promoters.

AB - Hox proteins form complexes with Pbx and Meis cofactors to control gene expression, but the role of Meis is unclear. We demonstrate that Hoxb1-regulated promoters are highly acetylated on histone H4 (AcH4) and occupied by Hoxb1, Pbx, and Meis in zebrafish tissues where these promoters are active. Inhibition of Meis blocks gene expression and reduces AcH4 levels at these promoters, suggesting a role for Meis in maintaining AcH4. Within Hox transcription complexes, Meis binds directly to Pbx and we find that this binding displaces histone deacetylases (HDACs) from Hoxb1-regulated promoters in zebrafish embryos. Accordingly, Pbx mutants that cannot bind Meis act as repressors by recruiting HDACs and reducing AcH4 levels, while Pbx mutants that bind neither HDAC nor Meis are constitutively active and recruit CBP to increase AcH4 levels. We conclude that Meis acts, at least in part, by controlling access of HDAC and CBP to Hox-regulated promoters.

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