Identification of novel PPARγ target genes by integrated analysis of ChIP-on-chip and microarray expression data during adipocyte differentiation

Nakachi, Yutaka; Yagi, Ken; Nikaido, Itoshi; Bono, Hidemasa; Tonouchi, Mio; Schönbach, Christian; Okazaki, Yasushi

doi:10.1016/j.bbrc.2008.05.037

Cited by 52 publications

(42 citation statements)

References 16 publications

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“…Such findings underscore the advantages of whole-genome approaches and the limitations of current methods searching for factor binding within gene promoters, including promoter bashing and promoter tiling arrays. In fact, a recent study involving adipocyte PPAR␥ ChIP and hybridization to a proximal promoter tiling array discovered only 167 binding sites while interrogating 16,592 promoters (Nakachi et al 2008).…”

Section: Discussionmentioning

confidence: 99%

“…These conclusions are based on analysis of only ∼30 genes identified as PPAR␥ targets through reporter gene and gel shift assays and chromatin immunoprecipitation (ChIP) (Tontonoz et al 1994a;IJpenberg et al 1997;Robinson et al 1998;Teboul et al 2001;Chui et al 2005;Guan et al 2005;Yajima et al 2007;Nakachi et al 2008). In contrast, expression profiling studies during adipocyte differentiation and following PPAR␥ ligand treatment suggest that hundreds of genes may be regulated by PPAR␥ (Perera et al 2006;Sears et al 2007;Nakachi et al 2008). Thus, the full range of PPAR␥-binding sites in adipocytes, or cistrome (Lupien et al 2008), remains largely unknown.…”

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confidence: 99%

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PPARγ and C/EBP factors orchestrate adipocyte biology via adjacent binding on a genome-wide scale

Lefterova¹,

Zhang²,

Steger³

et al. 2008

Genes Dev.

732

693

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Peroxisome proliferator-activated receptor ␥(PPAR␥), a nuclear receptor and the target of anti-diabetic thiazolinedione drugs, is known as the master regulator of adipocyte biology. Although it regulates hundreds of adipocyte genes, PPAR␥ binding to endogenous genes has rarely been demonstrated. Here, utilizing chromatin immunoprecipitation (ChIP) coupled with whole genome tiling arrays, we identified 5299 genomic regions of PPAR␥ binding in mouse 3T3-L1 adipocytes. The consensus PPAR␥/RXR␣ "DR-1"-binding motif was found at most of the sites, and ChIP for RXR␣ showed colocalization at nearly all locations tested. Bioinformatics analysis also revealed CCAAT/enhancer-binding protein (C/EBP)-binding motifs in the vicinity of most PPAR␥-binding sites, and genome-wide analysis of C/EBP␣ binding demonstrated that it localized to3350 of the locations bound by PPAR␥. Importantly, most genes induced in adipogenesis were bound by both PPAR␥ and C/EBP␣, while very few were PPAR␥-specific. C/EBP␤ also plays a role at many of these genes, such that both C/EBP␣ and ␤ are required along with PPAR␥ for robust adipocyte-specific gene expression. Thus, PPAR␥ and C/EBP factors cooperatively orchestrate adipocyte biology by adjacent binding on an unanticipated scale.[Keywords: PPAR␥; C/EBP; adipocyte; genome wide; ChIP-chip] Supplemental material is available at http://www.genesdev.org.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

PPARγ and C/EBP factors orchestrate adipocyte biology via adjacent binding on a genome-wide scale

Lefterova¹,

Zhang²,

Steger³

et al. 2008

Genes Dev.

732

693

View full text Add to dashboard Cite

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“…These genes include those encoding adipocyte lipid-binding protein 2 (aP2), fatty acidbinding protein 4, and lipoprotein lipase. Recent genomewide microarray and chromatin immunoprecipitation (ChIP) analyses have identified several other PPAR␥ target genes (5)(6)(7)(8)(9).…”

mentioning

confidence: 99%

Additional Sex Comb-like (ASXL) Proteins 1 and 2 Play Opposite Roles in Adipogenesis via Reciprocal Regulation of Peroxisome Proliferator-activated Receptor γ

Park

Yoon

Park

et al. 2011

Journal of Biological Chemistry

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Our previous studies have suggested that the mammalian additional sex comb-like 1 protein functions as a coactivator or repressor of retinoic acid receptors in a cell-specific manner. Here, we investigated the roles of additional sex comb-like 1 proteins in regulating peroxisome proliferator-activated receptors (PPARs). In pulldown assays in vitro and in immunoprecipitation assays in vivo, ASXL1 and its paralog, ASXL2, interacted with PPAR␣ and PPAR␥. In 3T3-L1 preadipocyte cells, overexpression of ASXL1 inhibited the induction of PPAR␥ activity by rosiglitazone, as shown by transcription assays, and completely suppressed adipogenesis, as shown by Oil Red O staining. In contrast, overexpression of ASXL2 greatly enhanced rosiglitazone-induced PPAR␥ activity and enhanced adipogenesis. Deletion of the heterochromatin protein 1 (HP1)-binding domain from ASXL1 caused the mutant protein to enhance adipogenesis similarly to ASXL2, indicating that HP1 binding is required for the adipogenesis-suppressing activity of ASXL1. Adipocyte differentiation was associated with a gradual decrease in ASXL1 expression but did not affect ASXL2 expression. Knockdown of ASXL1 and ASXL2 had reciprocal effects on adipogenesis. In chromatin immunoprecipitation assays in 3T3-L1 cells, ASXL1 occupied the promoter of the PPAR␥ target gene aP2 together with HP1␣ and Lys-9-methylated histone H3, whereas ASXL2 occupied the aP2 promoter together with histone-lysine N-methyltransferase MLL1 and Lys-9-acetylated and Lys-4-methylated H3 histones. Finally, microarray analysis demonstrated that ASXL1 represses, whereas ASXL2 increases, the expression of adipogenic genes, most of which are PPAR␥ targets. These results suggest that members of the additional sex comb-like family provide complex regulation of adipogenesis via differential modulation of PPAR␥ activity.

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“…3C and Table 4). Srebf1 is a known regulator of Fasn and Fabp4 transcription (Latasa et al, 2003;Nakachi et al, 2008).…”

Section: Effects Of Prenatal Bap Exposure and Gclm Genotype On Hepatimentioning

confidence: 99%

Reprint of “In utero exposure to benzo[a]pyrene increases adiposity and causes hepatic steatosis in female mice, and glutathione deficiency is protective”

Ortíz

Nakamura

et al. 2014

Toxicology Letters

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Identification of novel PPARγ target genes by integrated analysis of ChIP-on-chip and microarray expression data during adipocyte differentiation

Cited by 52 publications

References 16 publications

PPARγ and C/EBP factors orchestrate adipocyte biology via adjacent binding on a genome-wide scale

PPARγ and C/EBP factors orchestrate adipocyte biology via adjacent binding on a genome-wide scale

Additional Sex Comb-like (ASXL) Proteins 1 and 2 Play Opposite Roles in Adipogenesis via Reciprocal Regulation of Peroxisome Proliferator-activated Receptor γ

Reprint of “In utero exposure to benzo[a]pyrene increases adiposity and causes hepatic steatosis in female mice, and glutathione deficiency is protective”

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