A chromatin perspective of adipogenesis

Musri, Melina M.; Gomis, Ramón; Párrizas, Marcelina

doi:10.4161/org.6.1.10226

Cited by 34 publications

(29 citation statements)

References 121 publications

(191 reference statements)

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“…These two factors are between them responsible for the transcription of the largest part of adipocyte-specific genes, including the hormone adiponectin (apm1) or the transporters fabp4 and glut4. A number of recent studies have demonstrated the crucial role of epigenetic mechanisms in adipogenesis (for review, see 24). In our laboratory, we described a role for histone H3K4 dimethylation in labeling specific adipocyte genes such as apm1 as "poised" for transcription in undifferentiated fibroblasts that do not yet express them (25).…”

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confidence: 78%

Histone Demethylase LSD1 Regulates Adipogenesis

Musri¹,

Carmona

Hanzu

et al. 2010

Journal of Biological Chemistry

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143

128

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Epigenetic mechanisms, in particular the enzymatic modification of histones, are a crucial element of cell differentiation, a regulated process that allows a precursor cell basically to turn into a different cell type while maintaining the same genetic equipment. We have previously described that the promoters of adipogenic genes display significant levels of dimethylation at the Lys 4 of histone H3 (H3K4) in preadipocytes, where these genes are still silenced, thus maintaining the chromatin of the precursor cell in a receptive state. Here, we show that the expression of several histone demethylases and methyltransferases increases during adipogenesis, suggesting an important role for these proteins in this process. Knockdown of the H3K4/K9 demethylase LSD1 results in markedly decreased differentiation of 3T3-L1 preadipocytes. This outcome is associated with decreased H3K4 dimethylation and increased H3K9 dimethylation at the promoter of transcription factor cebpa, whose expression must be induced >200-fold upon stimulation of differentiation. Thus, our data suggest that LSD1 acts to maintain a permissive state of the chromatin in this promoter by opposing the action of a H3K9 methyltransferase. Knockdown of H3K9 methyltransferase SETDB1 produced the opposite results, by decreasing H3K9 dimethylation and increasing H3K4 dimethylation levels at the cebpa promoter and favoring differentiation. These findings indicate that the histone methylation status of adipogenic genes as well as the expression and function of the proteins involved in its maintenance play a crucial role in adipogenesis.

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confidence: 78%

Histone Demethylase LSD1 Regulates Adipogenesis

Musri¹,

Carmona

Hanzu

et al. 2010

Journal of Biological Chemistry

Self Cite

143

128

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“…Various histone modifications on PPAR␥-targeted adipogenic genes have been reported in both preadipocytes and adipocytes (recently reviewed in Ref. 46). These modifications occur either through the direct association of PPAR␥ with histone-modifying enzymes or through the indirect association of PPAR␥ with these enzymes via coregulators, resulting in differential PPAR␥ regulation and adipogenesis.…”

Section: Discussionmentioning

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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“…Pparγ cooperates with CCAAT/enhancer-binding proteins (C/EBP), including Cebpα, Cebpβ, and Cebpγ, to induce the expression of many genes important for terminal differentiation, such as Fabp4/aP2, Cd36, Lipe/Hsl, Olr1, and Me1 (6). Unlike transcriptional factors that bind to DNA directly, transcriptional cofactors often serve as molecular scaffolds to link the basal transcription machinery to either active or inactive complexes (7)(8)(9). Many cofactors, such as CBP and p300, have enzymatic activity in histone modification and can adjust chromatin environments to be more or less accessible to the transcription machinery.…”

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confidence: 99%

Long noncoding RNAs regulate adipogenesis

Sun

Goff

Trapnell

et al. 2013

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

387

338

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The prevalence of obesity has led to a surge of interest in understanding the detailed mechanisms underlying adipocyte development. Many protein-coding genes, mRNAs, and microRNAs have been implicated in adipocyte development, but the global expression patterns and functional contributions of long noncoding RNA (lncRNA) during adipogenesis have not been explored. Here we profiled the transcriptome of primary brown and white adipocytes, preadipocytes, and cultured adipocytes and identified 175 lncRNAs that are specifically regulated during adipogenesis. Many lncRNAs are adipose-enriched, strongly induced during adipogenesis, and bound at their promoters by key transcription factors such as peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (CEBPα). RNAi-mediated loss of function screens identified functional lncRNAs with varying impact on adipogenesis. Collectively, we have identified numerous lncRNAs that are functionally required for proper adipogenesis.

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A chromatin perspective of adipogenesis

Cited by 34 publications

References 121 publications

Histone Demethylase LSD1 Regulates Adipogenesis

Histone Demethylase LSD1 Regulates Adipogenesis

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

Long noncoding RNAs regulate adipogenesis

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