Biology subjects

Priyanka, P.

Publications and source records attributed to Priyanka, P..

3 recordsLinked to original sources

bioRxiv2026

Stress-Induced PTBP1 Reprograms Neuronal Function and Activates Cellular Senescence

Chronic oxidative stress is a major contributor to neuronal aging. Due to the lack of homologous recombination (HR) DNA damage repair, high oxygen consumption in neurons causes DNA damage accumulation with age, resulting in a decline in neuronal function, senescence-like phenotypes and onset of neurodegenerative diseases. Here, we identify increased PTBP1 as a stress-inducible negative regulator of neuronal gene expression and senescence-protectant genes. Oxidative stress robustly increases PTBP1 expression in ShSY-5Y differentiated neurons and primary mouse cortical neurons, coinciding with the loss of neuronal genes, including neuronal PTBP2, and activation of stress-responsive genes. Knockdown of PTBP1 in fibroblasts reduces the expression of key senescence genes. Transcriptomic analyses revealed that PTBP1 overexpression results in coordinated shift in gene expression characterized by repression of neuronal commitment genes and activation of stress and senescence genes. Mechanistically, PTBP1 induction is regulated by stress induced CTCF binding at the PTBP1 promoter. Together, our findings suggest that alteration in levels of PTBP1 acts as a molecular switch between neuronal function and survival, providing insight into transcriptional adaptations associated with aging. SUMMARYO_LILoss of PTBP1 in fibroblasts acts as a senescence protective gene C_LIO_LIxidative stress induces expression of PTBP1, reducing neuronal function gene expression and activating stress and cell cycle genes C_LIO_LIEctopic PTBP1 expression reprograms neuronal transcription, down-regulating cell fate commitment genes and activating a cell senescence program C_LIO_LIxidative stress induces PTBP1 and suppresses neuronal specific PTBP2 expression in primary cortical neurons C_LI

molecular biology↗

bioRxiv2024

Recruitment of CTCF to the SIRT1 promoter after Oxidative Stress mediates Cardioprotective Transcription

Because most DNA-binding transcription factors (dbTFs), including the architectural regulator CTCF, bind RNA and exhibit di-/multimerization, a central conundrum is whether these distinct properties are regulated post-transcriptionally to modulate transcriptional programs. Here, investigating stress-dependent activation of SIRT1, encoding an evolutionarily-conserved protein deacetylase, we show that induced phosphorylation of CTCF acts as a rheostat to permit CTCF occupancy of low-affinity promoter DNA sites to precisely the levels necessary. This CTCF recruitment to the SIRT1 promoter is eliciting a cardioprotective cardiomyocyte transcriptional activation program and provides resilience against the stress of the beating heart in vivo. Mice harboring a mutation in the conserved low-affinity CTCF promoter binding site exhibit an altered, cardiomyocyte-specific transcriptional program and a systolic heart failure phenotype. This transcriptional role for CTCF reveals that a covalent dbTF modification regulating signal-dependent transcription serves as a previously unsuspected component of the oxidative stress response.

cell biology↗

bioRxiv2018

Sex Determination in the garden lizard, Calotes versicolor: Is Environment a Factor?

The Indian garden lizard, C. versicolor, is known to lack sex chromosomes (Singh, 1974, Ganesh et al 1997). A report from the tropical southern India (Inamdar et al., 2012), claims a TSD (FMFM) mechanism in this species in which the male/female ratio in embryos oscillates within a range of 3-4{degrees}C. The present study presents results of experiments done in 4 consecutive breeding seasons of C. versicolor belonging to the subtropical/temperate climate of northern region of India. Eggs were grown at different temperatures (at 24.5/28/31.5{degrees}C) or under seminatural conditions. Another set of eggs was exposed to fadrozol, an aromatase inhibitor (AI), or Lithium Chloride (inhibitor of GSK3 enzyme inducing Wnt4-dependent Beta-Catenin). Results confirm our earlier finding that in this subtropical population of C. versicolor, temperature does not regulate gonadal differentiation but AI-induces sex reversal to the male sex (Ganesh and Raman, 1995, Ganesh et al 1999). We also report lack of any effect of Sox9 inhibitor on sexual differentiation which may be due to inadequate quantity or mode of application. Importantly, we report the serendipitous observation that in each year almost all the embryos/hatchlings were of the same sex ( females in 2013, 15, 16 and males in 2014) regardless of the rearing condition and duration of incubation. Obviously, parthenogenesis is not the cause of it. In the absence of an obvious reason to explain this pattern, we surmise that in this north Indian population of C. versicolor, female is the default sex, and certain epigenetic regulators could modulate the sexual differentiation of the individual.

developmental biology↗