Although transmission of the gene expression program from mother to daughter cells has been suggested to be mediated by gene bookmarking, the precise mechanism by which bookmarking mediates post-mitotic transcriptional re-activation has been unclear. Here, we used a real-time gene expression system to quantitatively demonstrate that transcriptional activation of the same genetic locus occurs with a significantly more rapid kinetics in post-mitotic cells versus interphase cells. RNA polymerase II large subunit (Pol II) and Bromodomain Protein 4 (BRD4) were recruited to the locus in a different sequential order upon interphase initiation versus post-mitotic re-activation resulting from the recognition by BRD4 of increased levels of histone H4 lysine 5 acetylation (H4K5Ac) on the previously activated locus. BRD4 accelerated the dynamics of mRNA synthesis by de-compacting chromatin and hence facilitating transcriptional reactivation. Together, using a real-time quantitative approach, we identified differences in the kinetics of transcriptional activation between interphase and post-mitotic cells that are mediated by a chromatin-based epigenetic mechanism.

SummaryThe eukaryotic nucleus is a highly compartmentalized and dynamic environment. Chromosome territories are arranged non-randomly within the nucleus and numerous studies have indicated that a gene's position in the nucleus can impact its transcriptional activity. Here, we focus on recent advances in our understanding of the influence of specific nuclear neighborhoods on gene expression or repression. Nuclear neighborhoods associated with transcriptional repression include the inner nuclear membrane/nuclear lamina and peri-nucleolar chromatin, whereas neighborhoods surrounding the nuclear pore complex, PML nuclear bodies, and nuclear speckles seem to be transcriptionally permissive. While nuclear position appears to play an important role in gene expression, it is likely to be only one piece of a flexible puzzle that incorporates numerous parameters. We are still at a very early, yet exciting stage in our journey toward deciphering the mechanism(s) that govern the permissiveness of gene expression/repression within different nuclear neighborhoods.

The ubiquitous expression in many organs throughout the body and the ability to respond to a wide variety of physical and chemical stimuli have brought transient receptor potential (TRP) channels to the vanguards of our sensory systems. TRP vanilloid-1 (TRPV1) is the founding member of the TRPV subfamily. TRPV1 can be activated by noxious heat, protons, and vanilloids. Previous studies have shown that TRPV1 is located on the plasma membrane, serving to non-selectively permeate calcium ion from the extracellular region to the cytoplasm. Interestingly, increasing evidence suggests that TRPV1 is also located intracellularly in various cell types such as neurons, myocytes, and numerous cancer cells. By immunocytochemistry and/or fractionation followed by Western blotting, TRPV1 was found to express on the endoplasmic reticulum/sarcoplasmic reticulum and the mitochondria. By using various pharmacological and molecular tools, intracellular TRPV1 was also found to functionally express to control calcium level both inside the organelles and in the cytoplasm. Recent studies have shown that intracellularly located TRPV1 serves versatile functions in various physiological and pathological conditions (e.g., exercise endurance and hypertrophy). In this review, we not only have summarized the well-characterized roles of TRPV1, but also have highlighted the increasing importance of intracellular TRPV1-mediated pathways. Lastly, we have pointed out future research direction for answering several important questions that have remained unanswered. Vigorous investigation of the emerging roles of intracellular TRPV1 can allow a better understanding of how TRPV1 controls the cellular calcium homeostasis and its role in various physiological and pathophysiological conditions. J. Cell. Physiol. 232: 1957-1965, 2017. © 2016 Wiley Periodicals, Inc.

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