IL-1 beta increases abundance and activity of the negative transcriptional regulator yin yang-1 (YY1) in neonatal rat cardiac myocytes

TY - JOUR

T1 - IL-1 beta increases abundance and activity of the negative transcriptional regulator yin yang-1 (YY1) in neonatal rat cardiac myocytes

AU - Patten, M

AU - Wang, W

AU - Aminololama-Shakeri, S

AU - Burson, M

AU - Long, C S

N1 - Copyright 2000 Academic Press.

PY - 2000/7

Y1 - 2000/7

N2 - Current research from both clinical and basic science perspectives indicates that cytokines play an important role in the genesis of cardiovascular pathology. Specifically, levels of cytokines such as interleukin-1 (IL-1), tumor necrosis factor- alpha (TNF- alpha), and interleukin-6 (IL-6) have been found to be elevated in both acute myocardial injury as well as situations of chronic dysfunction. Further, therapies directed primarily at interfering with cytokine action have suggested that such an immunomodulatory approach may be beneficial in some of these circumstances of myocardial injury. We recently reported that IL-1 beta induces a hypertrophic state in cultured neonatal rat cardiac myocytes that differs from other well described hypertrophic phenotypes in terms of myocardial gene expression (such as skeletal alpha -actin, sACT), an effect that appeared to co-localize with that of the negative regulator yin yang-1 (YY1).(1)In the present study, we further localize the area in the sACT promoter responsible for the IL-1 effect. These investigations indicate that sequences in and around the third upstream serum response element (SRE3) bind YY1 and are required for IL-1 beta mediated repression. This element is also capable of transferring both IL-1 beta and YY1-mediated transcriptional repression to a heterologous promoter. In support of an IL-1 beta induced post-translational modification of YY1 that results in an increase in DNA-binding activity,(32)P-labeling experiments reveal an increase in phosphorylated YY1 in IL-1 beta treated cells and phosphatase-treated myocyte nuclear proteins lose their ability to bind to the YY1 site. In summary, these results provide evidence that sequences within the SRE3 of the skeletal actin promoter represent an IL-1 beta response element and suggest that IL-1 beta activates the negative transcription factor YY1 by both transcriptional and post-transcriptional mechanisms.

AB - Current research from both clinical and basic science perspectives indicates that cytokines play an important role in the genesis of cardiovascular pathology. Specifically, levels of cytokines such as interleukin-1 (IL-1), tumor necrosis factor- alpha (TNF- alpha), and interleukin-6 (IL-6) have been found to be elevated in both acute myocardial injury as well as situations of chronic dysfunction. Further, therapies directed primarily at interfering with cytokine action have suggested that such an immunomodulatory approach may be beneficial in some of these circumstances of myocardial injury. We recently reported that IL-1 beta induces a hypertrophic state in cultured neonatal rat cardiac myocytes that differs from other well described hypertrophic phenotypes in terms of myocardial gene expression (such as skeletal alpha -actin, sACT), an effect that appeared to co-localize with that of the negative regulator yin yang-1 (YY1).(1)In the present study, we further localize the area in the sACT promoter responsible for the IL-1 effect. These investigations indicate that sequences in and around the third upstream serum response element (SRE3) bind YY1 and are required for IL-1 beta mediated repression. This element is also capable of transferring both IL-1 beta and YY1-mediated transcriptional repression to a heterologous promoter. In support of an IL-1 beta induced post-translational modification of YY1 that results in an increase in DNA-binding activity,(32)P-labeling experiments reveal an increase in phosphorylated YY1 in IL-1 beta treated cells and phosphatase-treated myocyte nuclear proteins lose their ability to bind to the YY1 site. In summary, these results provide evidence that sequences within the SRE3 of the skeletal actin promoter represent an IL-1 beta response element and suggest that IL-1 beta activates the negative transcription factor YY1 by both transcriptional and post-transcriptional mechanisms.

KW - Actins/genetics

KW - Animals

KW - Animals, Newborn

KW - Binding Sites

KW - Blotting, Western

KW - Cells, Cultured

KW - DNA/metabolism

KW - DNA-Binding Proteins/genetics

KW - Electrophoresis, Polyacrylamide Gel

KW - Erythroid-Specific DNA-Binding Factors

KW - Interleukin-1/pharmacology

KW - Mice

KW - Muscle, Skeletal/metabolism

KW - Myocardium/metabolism

KW - Phosphorylation

KW - Plasmids

KW - Promoter Regions, Genetic

KW - RNA, Messenger/metabolism

KW - Rats

KW - Repressor Proteins/metabolism

KW - Transcription Factors/genetics

KW - Transcription, Genetic

KW - Transfection

KW - YY1 Transcription Factor

KW - Zinc Fingers

U2 - 10.1006/jmcc.2000.1169

DO - 10.1006/jmcc.2000.1169

M3 - SCORING: Journal article

C2 - 10860774

VL - 32

SP - 1341

EP - 1352

JO - J MOL CELL CARDIOL

JF - J MOL CELL CARDIOL

SN - 0022-2828

IS - 7

ER -