Thyroid Hormone Stimulates Acetyl-CoA Carboxylase-α Transcription in Hepatocytes by Modulating the Composition of Nuclear Receptor Complexes Bound to a Thyroid Hormone Response Element

Zhang, Yanqiao; Yin, Liya; Hillgartner, F. Bradley

doi:10.1074/jbc.m005894200

Cited by 52 publications

(52 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The ACACA gene is regulated by thyroid hormone and encodes the ACACA subunit involved in fatty acid biosynthesis (24). It originally was identified in lipogenic tissue (liver and adipose tissue) (25) and is the rate-limiting enzyme in the biogenesis of long-chain fatty acids.…”

Section: Discussionmentioning

confidence: 99%

Diagnostic tool for the identification of MLL rearrangements including unknown partner genes

Meyer

Schneider

Reichel

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

169

157

View full text Add to dashboard Cite

Approximately 50 different chromosomal translocations of the human MLL gene are currently known and associated with high-risk acute leukemia. The large number of different MLL translocation partner genes makes a precise diagnosis a demanding task. After their cytogenetic identification, only the most common MLL translocations are investigated by RT-PCR analyses, whereas infrequent or unknown MLL translocations are excluded from further analyses. Therefore, we aimed at establishing a method that enables the detection of any MLL rearrangement by using genomic DNA isolated from patient biopsy material. This goal was achieved by establishing a universal longdistance inverse-PCR approach that allows the identification of any kind of MLL rearrangement if located within the breakpoint cluster region. This method was applied to biopsy material derived from 40 leukemia patients known to carry MLL abnormalities. Thirty-six patients carried known MLL fusions (34 with der(11) and 2 with reciprocal alleles), whereas 3 patients were found to carry novel MLL fusions to ACACA, SELB, and SMAP1, respectively. One patient carried a genomic fusion between MLL and TIRAP, resulting from an interstitial deletion. Because of this interstitial deletion, portions of the MLL and TIRAP genes were deleted, together with 123 genes located within the 13-Mbp interval between both chromosomal loci. Therefore, this previously undescribed diagnostic tool has been proven successful for analyzing any MLL rearrangement including previously unrecognized partner genes. Furthermore, the determined patientspecific fusion sequences are useful for minimal residual disease monitoring of MLL associated acute leukemias.acute leukemia ͉ MLL translocations ͉ translocation partner genes C hromosomal translocations involving the human MLL gene are recurrently associated with high-risk acute leukemias (1-4). MLL translocations correlate with specific disease subtypes (acute myeloid and acute lymphocytic leukemias), a specific gene expression profile (5, 6), and outcome (favorable or poor), depending on the particular MLL fusion (7). Approximately 50 different MLL translocation partner genes have been identified, suggesting that the human MLL gene is a hot spot for illegitimate recombination events. During illegitimate recombination events, one MLL allele is reciprocally fused with one of the many translocation partner genes. The latter encode nuclear or cytosolic proteins that share only a little sequence homology; however, the fused portion of partner protein sequences is necessary to confer oncogenic potential.The unambiguous identification of these MLL translocations is necessary to support rapid clinical decisions and specific therapy regimens. Current procedures to diagnose MLL rearrangements include cytogenetic analysis, FISH experiments (e.g., split-signal FISH) (8), and specific RT-PCR methods. However, results of RT-PCR analyses are influenced strongly by the quality of the investigated RNA samples. Furthermore, only the most frequent MLL fusions routine...

show abstract

Section: Discussionmentioning

confidence: 99%

Diagnostic tool for the identification of MLL rearrangements including unknown partner genes

Meyer

Schneider

Reichel

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

169

157

View full text Add to dashboard Cite

show abstract

“…Chick embryo hepatocytes were transfected as described by Zhang, Yin, and Hillgartner (29). Briefly, cells were isolated and incubated on 60 mm Petri dishes.…”

Section: Transient Transfectionmentioning

confidence: 99%

Chenodeoxycholic acid suppresses the activation of acetyl-coenzyme A carboxylase-α gene transcription by the liver X receptor agonist T0-901317

Talukdar

Bhatnagar

Dridi

et al. 2007

Journal of Lipid Research

Self Cite

View full text Add to dashboard Cite

The therapeutic utility of liver X receptor (LXR) agonists in treating atherosclerosis is limited by an undesired accumulation of triglycerides in the blood and liver. This effect is caused by an increase in the transcription of genes involved in fatty acid synthesis. Here, we show that the primary bile acid, chenodeoxycholic acid (CDCA), antagonizes the stimulatory effect of the synthetic LXR agonist, T0-901317, on the expression of acetyl-coenzyme A carboxylase-a (ACCa) and other lipogenic enzymes in chick embryo hepatocyte cultures. CDCA inhibits T0-901317-induced ACCa transcription by suppressing the enhancer activity of a LXR response unit (2101 to 271 bp) that binds LXR and sterol-regulatory element binding protein-1 (SREBP-1). We also demonstrate that CDCA decreases the expression of SREBP-1 in the nucleus and the acetylation of histone H3 and H4 at the ACCa LXR response unit. The CDCA-mediated reduction in ACCa expression is associated with a decrease in the expression of peroxisome proliferatoractivated receptor g coactivator-1a (PGC-1a) and small heterodimer partner and an increase in the expression of fibroblast growth factor-19 (FGF-19). Ectopic expression of FGF-19 decreases T0-901317-induced ACCa expression. Inhibition of p38 mitogen-activated protein kinase (MAPK) and/ or extracellular signal-regulated kinase (ERK) suppresses the effects of CDCA on the expression of ACCa, SREBP-1, PGC1a, and FGF-19. These results demonstrate that CDCA inhibits T0-901317-induced ACCa transcription by suppressing the activity of LXR and SREBP-1. We postulate that p38 MAPK, ERK, PGC-1a, and FGF-19 are components of the signaling pathway(s) mediating the regulation of ACCa gene transcription by CDCA.-Talukdar, S., S. Bhatnagar, S. Dridi, and F. B. Hillgartner. Chenodeoxycholic acid suppresses the activation of acetyl-coenzyme A carboxylase-a gene transcription by the liver X receptor agonist T0-901317. J. Lipid Res.

show abstract

“…PII is also lactationally stimulated in the mammary gland of the rat (Lopez-Casillas et al 1991) and is presumably important for the generation of milk fat in this species. Both chicken promoters were shown to be regulated by thyroid hormone, glucagon and medium-chain fatty acid (Yin et al 2000, Zhang et al 2001.…”

Section: Introductionmentioning

confidence: 99%

STAT5 binding contributes to lactational stimulation of promoter III expressing the bovine acetyl-CoA carboxylase alpha-encoding gene in the mammary gland

Mao¹,

Molenaar²,

Wheeler³

et al. 2002

Journal of Molecular Endocrinology

View full text Add to dashboard Cite

Activity of acetyl-CoA carboxylase (ACC)-α is rate limiting for de novo synthesis of fatty acids. The encoding gene is expressed by three different promoters. We characterized promoter III (PIII) from cow, previously only known from sheep. Quantitation of transcripts by RNAse protection assays and real time PCR revealed that PIII is primarily expressed and strongly induced (∼28-fold) in the lactating mammary gland. PIII transcripts are expressed in mammary epithelial cells (MEC) as shown by in situ hybridization. A 2999 bp segment of the PIII promoter conferred prolactin and dexamethasone inducibility to a luciferase reporter gene in stably transfected mouse MEC cells. Lactogenic induction was abolished if a unique signal transducer and activator of transcription (STAT)-binding site at position -797 was inactivated by two point mutations. An oligonucleotide probe harboring this STAT-site specifically bound nuclear proteins from the lactating mammary gland. Binding was abolished by those two point mutations and super-shift analyses showed that STAT5A factors are present in this complex. Hence, prolactin, acting through STAT5, contributes to the activation of ACC expression in the milk producing cells of the lactating mammary gland. We discuss that STAT5 might be important in determining the milk composition by coordinating fatty acid and protein synthesis during lactation.

show abstract

Thyroid Hormone Stimulates Acetyl-CoA Carboxylase-α Transcription in Hepatocytes by Modulating the Composition of Nuclear Receptor Complexes Bound to a Thyroid Hormone Response Element

Cited by 52 publications

References 62 publications

Diagnostic tool for the identification of MLL rearrangements including unknown partner genes

Diagnostic tool for the identification of MLL rearrangements including unknown partner genes

Chenodeoxycholic acid suppresses the activation of acetyl-coenzyme A carboxylase-α gene transcription by the liver X receptor agonist T0-901317

STAT5 binding contributes to lactational stimulation of promoter III expressing the bovine acetyl-CoA carboxylase alpha-encoding gene in the mammary gland

Contact Info

Product

Resources

About