Nuclear Architecture

We are focused on the study of different aspects of nuclear factors that modulate the organization of the nuclear architecture as well as the regulation of transcription during the process of adipocyte differentiation. We have presented evidence indicating that C/EBPβ, a key transcription factor for adipogenesis, is present in three different nuclear compartments: centromeric heterochromatin, euchromatin, and the nuclear matrix. This differential subnuclear distribution is likely to restrict its interaction with HP1α in precise nuclear domains which ultimately may have different functional consequences by controlling its bioavailability and transcriptional capacity. We have also been pioneers in the study of the high molecular weight immunophilin FKBP51 in adipogenesis. FKBP51 localizes in mitochondria an undergoes a rapid and dynamic relocalization to the nucleus dependent on PKA signaling at the onset of adipogenesis. In the nucleus, FKBP51 participates in the reorganization of the nuclear lamina as well as, in the control of the subnuclear distribution of the glucocorticoid receptor (GR) and the expression of GR target genes. It is important to highlight that glucocorticoids are required for proper adipogenesis and the remodeling of adipose tissue under different stimuli. Due to the high level of expression of FKBP51 in different fat depots, we are currently studying its role in the physiology of the adipose cell, i.e. in lipolysis and lipogenesis. In the last few years, we have extended our studies to the field of the long non-coding RNAs TERRAs (Telomeric Repeat-containing RNA) finding that their levels of expression increase in response to physiologic reactive oxygen species (ROS) signaling, as well as, upon DNA damage in telomeres caused by oxidative stress, situation that is also present in adipose tissue of obese individuals and the adipose cell associated to a tumor. We found that TERRAs increase in brown adipose tissue and white adipose tissue that undergoes browning in mice that were exposed to cold, due to the increase of mitochondrial ROS required for proper thermogenesis. It is very important to expand the study of TERRAs to uncover their role in the nucleus as possible modulator of genes that are distant from telomeres and related with different aspects of the biology of the adipose cells