Acetylation and deacetylation regulate CCAAT/enhancer binding protein β at K39 in mediating gene transcription

Ceseña, Teresa I.; Cui, Tracy X.; Subramanian, Lalitha; Fulton, Christina T.; Iñiguez‐Lluhí, Jorge A.; Kwok, Roland P.S.; Schwartz, Jessica

doi:10.1016/j.mce.2008.03.009

Cited by 35 publications

(36 citation statements)

References 48 publications

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“…The finding that dominant negative NF-YA29 and A-C/EBP␤ significantly decreases RGS4 promoter activity in confluent cells supports this model. Acetylation of C/EBP␤ has also been implicated in enhancing its transcriptional activity in adipose tissue (45). However, we found that TSA treatment had little effect on the binding of C/EBP␤ to the RGS4 promoter.…”

Section: Discussionmentioning

confidence: 51%

“…Acetylation of NF-YA and Bcl6 Regulates RGS4 Promoter ActivityIn view of recent evidence that acetylation of NF-YA (32), C/EBP␤ (44,45), and Bcl6 (46) can modulate their transcriptional activities, we undertook studies to determine whether acetylation of these transcription factors was associated with activation of the RGS4 promoter at cellular confluency. Acetylation was assessed by immunoprecipitation of these proteins followed by anti-acetyl-lysine immunoblotting.…”

Section: Cell Density-dependent Transcriptional Activation Of Rgs4 Ismentioning

confidence: 99%

“…However, the observed increases in C/EBP␤ protein levels (2-4-fold) under these conditions were larger than the increases in its acetylation (1-fold or less). Ceseña et al (45) recently demonstrated that acetylation of C/EBP␤ enhances its transcriptional activity. Therefore, it is likely that increases in both acetylated and total C/EBP␤ protein are involved in its activation of the RGS4 promoter, with our subsequent studies (Fig.…”

Section: Cell Density-dependent Transcriptional Activation Of Rgs4 Ismentioning

confidence: 99%

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A Novel Mechanism Involving Coordinated Regulation of Nuclear Levels and Acetylation of NF-YA and Bcl6 Activates RGS4 Transcription

Yang

Huang

Chatterjee

et al. 2010

Journal of Biological Chemistry

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Neuronally enriched RGS4 plays a critical role attenuating G protein signaling in brain, although the mechanisms regulating RGS4 expression are unknown. Here we describe a novel mechanism for transcriptional activation of RGS4 in neuron-like PC6 cells, where RGS4 is markedly induced during confluence-induced growth arrest. Transcriptional activation of RGS4 in confluent PC6 cells was accompanied by impaired G i/o -dependent MAPK activation. In the human RGS4 gene promoter, we identified three phylogenetically conserved cis-elements: an inverted CCAAT box element (ICE), a cAMP response element, and a B-cell lymphoma 6 (Bcl6)-binding site. The ICE and the cAMP response element mediate activation, and the Bcl6 site mediates repression of RGS4 transcription. Activation of RGS4 transcription in confluent PC6 cells is accompanied by increases in NF-YA and C/EBP␤ and decreases in Bcl6 levels in the nucleus. Increases in NF-YA and C/EBP␤ lead to their increased binding to the RGS4 promoter in vivo, and dominant negative forms of these proteins repressed RGS4 promoter activity. Acetylation of NF-YA and Bcl6 were increased in postconfluent cells. Trichostatin A stimulation of RGS4 promoter activity, accompanied by increased binding of NF-YA and decreased binding of Bcl6 to the promoter, was abolished by mutation of the ICE and enhanced by mutation of the Bcl6 site. These findings demonstrate a dynamic and coordinated regulation of nuclear levels and acetylation status of trans-acting factors critical in determining the off/on state of the RGS4 promoter. Regulator of G protein signaling 4 (RGS4)2 is a member of the mammalian RGS family of proteins of which 30 members exist in humans. RGS proteins were discovered as essential negative regulators of heterotrimeric G protein signaling by genetic studies in yeast and Caenorhabditis elegans (1, 2). These proteins act as GTPase-activating proteins for heterotrimeric G ␣ subunits (3), thereby accelerating the shut-off mechanism for G protein signaling. Some RGS proteins, including RGS4, can also act as effector antagonists (4, 5) or can directly or indirectly interact with G protein-coupled receptors (6 -8), actions that contribute to their negative regulatory effects on G protein signaling in cells.Although G protein signaling is involved in virtually every known physiological process and RGS proteins are an important component of this signaling, the mechanisms regulating expression of RGS genes are largely unknown. Studies have shown that several RGS genes are induced under certain physiological conditions, for example RGS1 during mitogenic activation of lymphocytes (9), RGS2 in the early stage of 3T3-L1 differentiation to adipocytes (10), RGS16 during genotoxic stress (11), and the yeast RGS gene SST2 by pheromone (12). Regulation of RGS4 expression has also been noted in facial motoneuronal precursors during embryonic development in mice (13), in epithelial and endothelial cells during tubulogenesis (14), and in rat PC12 cells during cell confluence (15). In the study by Gril...

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Section: Discussionmentioning

confidence: 51%

Section: Cell Density-dependent Transcriptional Activation Of Rgs4 Ismentioning

confidence: 99%

Section: Cell Density-dependent Transcriptional Activation Of Rgs4 Ismentioning

confidence: 99%

See 1 more Smart Citation

A Novel Mechanism Involving Coordinated Regulation of Nuclear Levels and Acetylation of NF-YA and Bcl6 Activates RGS4 Transcription

Yang

Huang

Chatterjee

et al. 2010

Journal of Biological Chemistry

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“…Post-transcriptional modifications such as phosphorylations, SUMOylations, and acetylations have been shown to affect C/EBPb activity (Ramji & Foka 2002, Berberich-Siebelt et al 2006, Cesena et al 2008, Khanna-Gupta 2008. For instance, EGF simulation in vitro has been shown to repress transcription of COX2 via sumoylation of C/EBPb (Wang et al 2008), as opposed to the other documented role of C/EBPb in promoting COX2 transcription (Hsu et al 2010).…”

Section: Post-transcriptional Modificationsmentioning

confidence: 99%

The emerging role of C/EBPs in glucocorticoid signaling: lessons from the lung

Roos¹,

Nord²

2011

Journal of Endocrinology

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Glucocorticoids (GCs) have been successfully used in the treatment of inflammatory diseases for decades. However, there is a relative GC resistance in several inflammatory lung disorders, such as chronic obstructive pulmonary disease (COPD), but still the mechanism(s) behind this unresponsiveness remains unknown. Interaction between transcription factors and the GC receptor contribute to GC effects but may also provide mechanisms explaining steroid resistance. CCAAT/enhancer-binding protein (C/EBP) transcription factors are important regulators of pulmonary gene expression and have been implicated in inflammatory lung diseases such as asthma, pulmonary fibrosis, cystic fibrosis, sarcoidosis, and COPD. In addition, several studies have indicated a role for C/EBPs in mediating GC effects. In this review, we discuss the different mechanisms of GC action as well as the function of the lung-enriched members of the C/EBP transcription factor family. We also summarize the current knowledge of the role of C/EBP transcription factors in mediating the effects of GCs, with emphasis on pulmonary effects, and their potential role in mediating GC resistance.

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“…C/EBP␤ can be phosphorylated (25), acetylated (26), and sumoylated (27). In this study, we find that C/EBP␤ is GlcNAcylated on Ser 180 180 and Ser 181 to alanine residues significantly increase the transcriptional activity of C/EBP␤.…”

mentioning

confidence: 99%