Related Experiment Video

Updated: Aug 8, 2026

Isolation and Differentiation of Stromal Vascular Cells to Beige/Brite Cells
07:22

Isolation and Differentiation of Stromal Vascular Cells to Beige/Brite Cells

Published on: March 28, 2013

Cyclin D1 inhibits peroxisome proliferator-activated receptor gamma-mediated adipogenesis through histone deacetylase

Maofu Fu1, Mahadev Rao, Toula Bouras

  • 1Lombardi Comprehensive Cancer Center, Department of Oncology, Georgetown University, Washington, D. C. 20057, USA.

The Journal of Biological Chemistry
|February 17, 2005
PubMed

Insights

Cyclin D1 regulates adipocyte differentiation by recruiting histone deacetylases (HDACs). This mechanism involves controlling chromatin structure at the PPAR response element, impacting gene expression and cell fate.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Gene Regulation

Background:

  • Cyclin D1 is a regulatory protein influencing cell proliferation and inhibiting adipocyte differentiation.
  • Cyclin D1's inhibition of peroxisome proliferator-activated receptor (PPAR)gamma activity occurs independently of its known kinase functions.
  • Understanding the precise molecular mechanism of cyclin D1's regulation of PPARgamma is crucial for elucidating adipogenesis control.

Purpose of the Study:

  • To elucidate the molecular mechanism by which cyclin D1 regulates PPARgamma function.
  • To investigate the role of histone deacetylases (HDACs) in cyclin D1-mediated inhibition of adipocyte differentiation.
  • To determine how cyclin D1 affects chromatin structure at PPAR response elements.

Main Methods:

  • Utilized murine embryonic fibroblasts (MEFs) lacking cyclin D1 (Cyclin D1-/- MEFs).
  • Assessed adipocyte differentiation, PPARgamma activity, and HDAC activity.
  • Employed co-immunoprecipitation and chromatin immunoprecipitation (ChIP) assays to study protein interactions and DNA binding.

Main Results:

  • Cyclin D1 deficiency in MEFs enhanced adipocyte differentiation and reduced HDAC1 activity.
  • Reintroducing cyclin D1 restored HDAC activity, inhibited PPARgamma-mediated adipogenesis, and enhanced HDAC repression of PPARgamma.
  • Cyclin D1 physically associated with multiple HDACs (HDAC1, HDAC2, HDAC3, HDAC5) and promoted their recruitment to the lipoprotein lipase promoter's PPAR response element, decreasing histone acetylation.

Conclusions:

  • Cyclin D1 plays a critical role in regulating PPARgamma-mediated adipocyte differentiation.
  • Cyclin D1 recruits HDACs to modulate local chromatin structure at PPAR response elements, thereby controlling PPARgamma function.
  • This mechanism highlights a novel pathway for regulating adipogenesis involving cyclin D1 and HDACs.

More Related Videos

Mechanism of Regulation of Adipocyte Numbers in Adult Organisms Through Differentiation and Apoptosis Homeostasis08:34

Mechanism of Regulation of Adipocyte Numbers in Adult Organisms Through Differentiation and Apoptosis Homeostasis

Published on: June 3, 2016

Measuring the Rate of Lipolysis in Ex Vivo Murine Adipose Tissue and Primary Preadipocytes Differentiated In Vitro09:41

Measuring the Rate of Lipolysis in Ex Vivo Murine Adipose Tissue and Primary Preadipocytes Differentiated In Vitro

Published on: March 17, 2023

Related Concept Videos

Positive Regulator Molecules01:45

Positive Regulator Molecules

To consistently produce healthy cells, the cell cycle—the process that generates daughter cells—must be precisely regulated.
Positive Regulator Molecules02:39

Positive Regulator Molecules

Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Anaphase Promoting Complex00:50

Anaphase Promoting Complex

The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of cells.
Two...
Inhibition of CDK Activity02:34

Inhibition of CDK Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...