TY - JOUR
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.
N1 - Funding Information:
We are grateful to L. Etheridge for assistance with experiments, to Y. Ohkawa and A. Imbalzano for assistance with the ChIP protocol, and to T. Kouzarides and R. Roeder for providing plasmids. This work was supported by NIH grant NS038183.
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.
KW - DEVBIO
UR - http://www.scopus.com/inward/record.url?scp=70349986266&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=70349986266&partnerID=8YFLogxK
U2 - 10.1016/j.devcel.2009.08.007
DO - 10.1016/j.devcel.2009.08.007
M3 - Article
C2 - 19853569
AN - SCOPUS:70349986266
SN - 1534-5807
VL - 17
SP - 561
EP - 567
JO - Developmental cell
JF - Developmental cell
IS - 4
ER -