Characterization of the Pal motifs in the upstream glucokinase promoter: binding of a cell type-specific protein complex correlates with transcriptional activation

1996 ◽  
Vol 10 (6) ◽  
pp. 723-731 ◽  
Author(s):  
J. M. Moates
2008 ◽  
Vol 28 (10) ◽  
pp. 3526-3537 ◽  
Author(s):  
Claudio Sustmann ◽  
Henrik Flach ◽  
Hanna Ebert ◽  
Quinn Eastman ◽  
Rudolf Grosschedl

ABSTRACT Transcriptional regulation by the canonical Wnt pathway involves the stabilization and nuclear accumulation of β-catenin, which assembles with LEF1/TCF transcription factors and cofactors to activate Wnt target genes. Recently, the nuclear β-catenin complex has been shown to contain BCL9, which interacts with β-catenin and recruits Pygopus as a transcriptional coactivator. However, the presumed general functions of Pygopus and BCL9, which has been proposed to act as a scaffolding protein for Pygopus, have been challenged by the rather specific and modest developmental defects of targeted inactivations of both the Pygo1 and the Pygo2 genes. Here, we analyze the function of BCL9 in transcriptional activation by β-catenin. We find that BCL9 acts in a cell-type-specific manner and, in part, independent of Pygopus. We show that BCL9 itself contains a transcriptional activation domain in the C terminus, which functionally synergizes in lymphoid cells with the C-terminal transactivation domain of β-catenin. Finally, we identify amino acids in the transactivation domain of β-catenin that are important for its function and association with the histone acetyltransferases CBP/p300 and TRRAP/GCN5. Thus, BCL9 may serve to modulate and diversify the transcriptional responses to Wnt signaling in a cell-type-specific manner.


2021 ◽  
Author(s):  
James M Gahan ◽  
Maria Hernandez-Valladares ◽  
Fabian Rentzsch

Chromatin-modifying proteins are key players in the regulation of development and cell differentiation in animals. Many individual chromatin modifiers, however, predate the evolution of animal multicellularity and how they became integrated into the regulatory networks underlying development is unclear. Here we show that CoREST is an animal-specific protein that assembles a conserved, vertebrate-like histone-modifying complex including Lsd1 and HDAC1/2 in the sea anemone Nematostella vectensis. We further show that NvCoREST expression overlaps fully with that of NvLsd1 throughout development. NvCoREST mutants, generated using CRISPR-Cas9, reveal essential roles during development and for the differentiation of cnidocytes, thereby phenocopying NvLsd1 mutants. We also show that this requirement is cell autonomous using a cell-type-specific rescue approach. Together, this shows that the evolution of CoREST allowed the formation of a chromatin-modifying complex that was present before the last common cnidarian-bilaterian ancestor and thus represents an ancient component of the animal developmental toolkit.


1987 ◽  
Vol 6 (5) ◽  
pp. 1339-1344 ◽  
Author(s):  
F. V. Swift ◽  
K. Bhat ◽  
H. B. Younghusband ◽  
H. Hamada

1999 ◽  
Vol 207 (2) ◽  
pp. 476
Author(s):  
Margit Mahlapuu ◽  
Markku Pelto-Huikko ◽  
Marjo Aitola ◽  
Sven Enerbäck ◽  
Peter Carlsson

1998 ◽  
Vol 202 (2) ◽  
pp. 183-195 ◽  
Author(s):  
Margit Mahlapuu ◽  
Markku Pelto-Huikko ◽  
Marjo Aitola ◽  
Sven Enerbäck ◽  
Peter Carlsson

Development ◽  
2001 ◽  
Vol 128 (14) ◽  
pp. 2833-2845 ◽  
Author(s):  
Thomas Marty ◽  
M. Alessandra Vigano ◽  
Carlos Ribeiro ◽  
Ute Nussbaumer ◽  
Nicole C. Grieder ◽  
...  

A central theme during development and homeostasis is the generation of cell type-specific responses to the action of a limited number of extant signaling cascades triggered by extracellular ligands. The molecular mechanisms by which information from such signals are integrated in responding cells in a cell-type specific manner remain poorly understood. We have undertaken a detailed characterization of an enhancer that is regulated by DPP signaling and by the homeotic protein Labial and its partners, Extradenticle and Homothorax. The expression driven by this enhancer (lab550) and numerous deletions and point mutants thereof was studied in wild-type and mutant Drosophila embryos as well as in cultured cells. We find that the lab550 enhancer is composed of two elements, a Homeotic Response Element (HOMRE) and a DPP Response Element (DPPRE) that synergize. None of these two elements can reproduce the expression of lab550, either with regard to expression level or with regard to spatial restriction. The isolated DPPRE of lab550 responds extremely weakly to DPP. Interestingly, we found that the inducibility of this DPPRE is weak because it is tuned down by the action of a repressor element. This repressor element and an additional 50 bp element appear to be crucial for the cooperation of the HOMRE and the DPPRE, and might tightly link the DPP response to the homeotic input. The cooperation between the different elements of the enhancer leads to the segmentally restricted activity of lab550 in the endoderm and provides a mechanism to create specific responses to DPP signaling with the help of a HOX protein complex.


2010 ◽  
Vol 39 (3) ◽  
pp. 455-467 ◽  
Author(s):  
Kasia G. Gora ◽  
Christos G. Tsokos ◽  
Y. Erin Chen ◽  
Balaji S. Srinivasan ◽  
Barrett S. Perchuk ◽  
...  

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