Deletion of the major GATA1 enhancer HS 1 does not affect eosinophil GATA1 expression and eosinophil differentiation

Blood ◽  
2004 ◽  
Vol 104 (1) ◽  
pp. 89-91 ◽  
Author(s):  
Boris Guyot ◽  
Veronica Valverde-Garduno ◽  
Catherine Porcher ◽  
Paresh Vyas

Abstract Expression of the myeloid transcription factor GATA1 is required for early stages of eosinophil differentiation. Defining mechanisms regulating eosinophil GATA1 expression will be important to understand development of this lineage. However, the cis-elements required for eosinophil GATA1 expression are not fully characterized. Previous work identified HS 1 as a major GATA1 enhancer, but its role in eosinophil GATA1 expression is unclear. Here, we show that mouse HS 1 deletion leaves eosinophil GATA1 mRNA expression and eosinophil differentiation unaffected. Chromatin isolated from eosinophils and encompassing HS 1 is weakly enriched for acetylated histones H3/H4. HS 1 deletion does not alter eosinophil GATA1 locus histone acetylation. In eosinophils, GATA1 and CCAAT/enhancer binding protein ϵ (C/EBPϵ) do not bind HS 1 but bind selectively a cis-element in the first GATA1 intron. Thus, HS 1 is not required for eosinophil GATA1 expression. Instead, this study suggests a previously unsuspected role for the GATA1 intron element for this function.

2001 ◽  
Vol 12 (11) ◽  
pp. 2221-2230 ◽  
Author(s):  
JUNG H. CHA ◽  
SEUNG KYOON WOO ◽  
KI H. HAN ◽  
YOUNG H. KIM ◽  
JOSEPH S. HANDLER ◽  
...  

Abstract. Tonicity responsive enhancer binding protein (TonEBP) is the transcription factor that regulates tonicity responsive expression of proteins that catalyze cellular accumulation of compatible osmolytes. In cultured MDCK cells, hypertonicity stimulates the activity of TonEBP via a combination of increased protein abundance and increased nuclear localization. For investigating regulation of TonEBP in the kidney, rats were subjected to water loading or dehydration. Water loading lowered urine osmolality and mRNA expression of sodium/myo-inositol cotransporter (SMIT), a target gene of TonEBP, in the renal medulla; dehydration doubled the urine osmolality and increased SMIT mRNA expression. In contrast, overall abundance of TonEBP and its mRNA measured by immunoblot and ribonuclease protection assay, respectively, was not affected. Immunohistochemical analysis, however, revealed that nuclear distribution of TonEBP is generally increased throughout the medulla in dehydrated animals compared with water loaded animals. Increased nuclear localization was particularly dramatic in thin limbs. Notable exceptions were the middle to terminal portions of the inner medullary collecting ducts and blood vessels, where a change in TonEBP distribution was not evident. Immunohistochemical detection of SMIT mRNA revealed that the changes in nuclear distribution of TonEBP correlate with expression of SMIT. It is concluded that under physiologic conditions, nucleocytoplasmic distribution is the dominant mode of regulation of TonEBP in the renal medulla.


2014 ◽  
Vol 45 (8) ◽  
pp. 919-932 ◽  
Author(s):  
Jörg C. Gerlach ◽  
Patrick Over ◽  
Hubert G. Foka ◽  
Morris E. Turner ◽  
Robert L. Thompson ◽  
...  

2005 ◽  
Vol 25 (5) ◽  
pp. 1971-1979 ◽  
Author(s):  
Kenji Hata ◽  
Riko Nishimura ◽  
Mio Ueda ◽  
Fumiyo Ikeda ◽  
Takuma Matsubara ◽  
...  

ABSTRACT Although both osteoblasts and adipocytes have a common origin, i.e., mesenchymal cells, the molecular mechanisms that define the direction of two different lineages are presently unknown. In this study, we investigated the role of a transcription factor, CCAAT/enhancer binding protein β (C/EBPβ), and its isoform in the regulation of balance between osteoblast and adipocyte differentiation. We found that C/EBPβ, which is induced along with osteoblast differentiation, promotes the differentiation of mesenchymal cells into an osteoblast lineage in cooperation with Runx2, an essential transcription factor for osteogenesis. Surprisingly, an isoform of C/EBPβ, liver-enriched inhibitory protein (LIP), which lacks the transcriptional activation domain, stimulates transcriptional activity and the osteogenic action of Runx2, although LIP inhibits adipogenesis in a dominant-negative fashion. Furthermore, LIP physically associates with Runx2 and binds to the C/EBP binding element present in the osteocalcin gene promoter. These data indicate that LIP functions as a coactivator for Runx2 and preferentially promotes the osteoblast differentiation of mesenchymal cells. Thus, identification of a novel role of the C/EBPβ isoform provides insight into the molecular basis of the regulation of osteoblast and adipocyte commitment.


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