The Socolovsky lab has identified an epigenetic switch that controls the transition from self-renewal to differentiation in erythroid progenitors.
Interestingly, this cell fate decision is orchestrated by the cell cycle and is associated with an unusual process in which there is global loss of genomicDNA methylation , the first such instance to be identified in somatic cells.
The Wolfe Lab focuses on multiple aspects of gene expression, including transcriptional and post-transcriptional control. They are also interested in developing new tools for targeted gene regulation.
In addition, the Wolfe Lab is part of the Innate Immune Gene Regulatory Project , a collaborative effort to understand the regulatory pathways that underpin the response of Dendritic cells to pathogens. Regarding post-transcriptional control of gene expression, they are focused on understanding the role of miR in pancreatic endocrine cell development using zebrafish as a model. The life and death of cells Modeling cancer Bioinformatics Editing the genome Finding new treatments for cancer What controls gene expression?
How do tumors grow and spread? Metabolism and disease Infection and disease. What controls gene expression? Bach Lab One of the main goals of the research carried out in the Bach lab is to understand mechanisms controlling gene expression during mammalian embryogenesis. Nature , Shin et al. RLIM is dispensable for X-chromosome inactivation in the mouse embryonic epiblast. Nature , Baehrecke Lab Our laboratory studies how steroid hormones control distinct types of cell responses within animal cells and tissues.
Genome-wide analyses of steroid- and radiation-triggered programmed cell death in Drosophila. Curr Biol. Mol Cell. Cell Jun 29; 1 The proton-coupled monocarboxylate transporter Hermes is necessary for autophagy during cell death. Dev Cell. Benanti Lab Cell proliferation is controlled by a tightly-regulated transcriptional program, which ensures that cells only proceed through the cell division cycle when they receive the appropriate signals.
Landry et al. EMBO J; Gene regulation also allows cells to react quickly to changes in their environments. Although we know that the regulation of genes is critical for life, this complex process is not yet fully understood. Signals from the environment or from other cells activate proteins called transcription factors.
These proteins bind to regulatory regions of a gene and increase or decrease the level of transcription. By controlling the level of transcription, this process can determine when and how much protein product is made by a gene. These genes generally transcribe continuously since the bacterium needs tryptophan. However, if tryptophan concentrations are high, transcription is repressed turned off by binding to a repressor protein and activating it as illustrated below. After fertilization, the cells in the developing embryo become increasingly specialized, largely by turning on some genes and turning off many others.
Each type of cell has a particular pattern of expressed genes. Gene expression in eukaryotes may also be regulated through by alterations in the packing of DNA, which modulates the access of the cell's transcription enzymes e. The illustration below shows that chromosomes have a complex structure. The DNA helix is wrapped around special proteins called histones, and this are wrapped into tight helical fibers.
In addition, there are many more regulatory proteins in eukaryotes and the interactions are much more complex. In eukaryotes transcription takes place within the membrane-bound nucleus, and the initial transcript is modified before it is transported from the nucleus to the cytoplasm for translation at the ribosome s. The profiles of the methylation of DNAs and the modifications, including acetylation and methylation of histones, are altered in the aging process [ 72 , 73 ].
These epigenetic changes will enhance or reduce transcription of specific genes. Cytokine dysregulation or prolonged inflammation is observed in aged person [ 74 ]. Numbers of proteins are involved in the inflammation process, suggesting that expression and degradation of proteins could accelerate or decelerate cellular senescence. Decline in metabolites, which target DNA-binding proteins and ncRNAs [ 46 , 47 , 48 ] to modulate epigenetic systems [ 24 , 25 , 26 , 27 , 28 , 29 , 30 ], would accelerate aging.
Given that alterations in the transcription could cause the aging, it could be slowed by manipulating TFs profile. Homeostasis or negative feedback is not only required for endocrine system but also for biochemical reactions. Metabolites, including sugars, lipids and amino acids, and ionic substrates need to be maintained within biologically significant level. Similarly, nucleic acids and proteins should be appropriately managed being continuously synthesized and degraded.
The equilibrium will gradually change in accordance with aging. Homeostasis in organs would play a role in the cancer generation [ 76 ]. Senescence can be metaphorically expressed as a walk on a balance beam that is narrowed afterward. The younger cells proliferate faster and respond to stresses with more accuracy than the older ones. After repeated proliferation, cells will reach the point where they cannot go forward but initiate aging.
Somatic cells can acquire a pluripotency by incorporation of TFs. So, is it not possible to reverse aged or abnormal cells into younger or healthy cells? Then, what molecules nucleic acids, proteins, etc.
That should be answered for the next-generation therapeutics against aging-related diseases Figure 1. Concept of the next-generation transcriptome-based therapeutics. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest.
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