Priyanka Sharma

• Ph.D (Biomedical Science)
• Researcher at Institute of Pharmacology and Structural Biology

Peptidyl arginine deiminases (PADIs) catalyze protein citrullination, a post-translational conversion of arginine to citrulline. The most widely expressed member of this family, PADI2, regulates cellular processes that impact several diseases. We hypothesized that we could gain new insights into PADI2 function through a systematic evolutionary and...

Peptidyl arginine deiminases (PADIs) catalyze protein citrullination, a post-translational conversion of arginine to citrulline. The most widely expressed member of this family, PADI2, regulates cellular processes that impact several diseases. We hypothesized that we could gain new insights into PADI2 function through a systematic evolutionary and...

Protein arginine deimination leading to the non-coded amino acid citrulline remains a key question in the field of post-translational modifications ever since its discovery by Rogers and Simmonds in 1958. Citrullination is catalyzed by a family of enzymes called peptidyl arginine deiminases (PADIs). Initially, increased citrullination was associate...

In breast cancer cells, some topologically associating domains (TADs) behave as hormonal gene regulation units, within which gene transcription is coordinately regulated in response to steroid hormones. Here we further describe that responsive TADs contain 20- to 100-kb-long clusters of intermingled estrogen receptor (ESR1) and progesterone recepto...

The post-translational modification of key residues at the C-terminal domain of RNA polymerase II (RNAP2-CTD) coordinates transcription, splicing, and RNA processing by modulating its capacity to act as a landing platform for a variety of protein complexes. Here, we identify a new modification at the CTD, the deimination of arginine and its convers...

In breast cancer cells, topologically associating domains (TADs) behave as units of hormonal gene regulation with transcripts within hormone responsive TADs changing coordinately their expression in response to steroid hormones. Here we further described that responsive TADs contain 20-100 kb-long clusters of intermingled estrogen receptor (ER) and...

The acquisition of cellular identity is coupled to changes in the nuclear periphery and nuclear pore complexes (NPCs). Whether and how these changes determine cell fate remain unclear. We have uncovered a mechanism that regulates NPC acetylation to direct cell fate after asymmetric division in budding yeast. The lysine deacetylase Hos3 associates s...

Highlights Peptidyl arginine deiminase 2 (PADI2) citrullinates arginine1810 (cit1810) present at carboxy-terminal domain of RNA polymerase II (RNAP2-CTD). PADI2 and R1810 of RNAP2-CTD regulate transcription and proliferation of breast cancer cells. Absence of cit1810 at RNAP2-CTD leads to RNAP2 accumulation at proximal promoter regions. Cit1810 at...

The acquisition of cellular identity is coupled to changes in the nuclear periphery and nuclear pore complexes (NPCs). Whether and how these changes determine cell fate remains unclear. We have uncovered a mechanism regulating NPC acetylation to direct cell fate after asymmetric division in budding yeast. The lysine deacetylase Hos3 associates spec...

Eukaryotic gene regulation is associated with changes in chromatin compaction that modulate access to DNA regulatory sequences relevant for transcriptional activation or repression. Although much is known about the mechanism of chromatin remodeling in hormonal gene activation, how repression is accomplished is much less understood. Here we report t...

Depletion of HP1 proteins reactivates HERVs and TNFα. (A) Total RNA from MCF7 cells transfected with the indicated small interfering RNAs (siRNAs) was quantified with RT-qPCR. Changes in mRNA levels are shown relative to the siGAPDH transfection (set to 1). The data are presented as the means ± SEM of triplicate experiments.(B and D) MCF7 cells wer...

Clinical and demographic data for the lymphocyte samples. The data given for age and duration (years), and EDSS are: mean (range). Abbreviations are as follows: MS: MS patient; U: unaffected relative; PP primary progressive MS; RR: relapsing-remitting MS; SP: secondary progressive MS; M: male; F: female; y: years; EDSS: expanded disability status s...

PADI4 expression and activity is induced in MCF7 cells by a treatment with estradiol and an ionophore. (A) Extracts from MCF7 cells treated either estradiol (E2) or ionophore (A23187) and/or both as indicated were analyzed by Western-blot with anti-PADI4 & anti-Brg1 antibodies. Blots are representative of the experimental replicates. (B) Treatment...

HP1α in the repression of HERVs and cytokines. Correlation matrix representing the correlation between the presence of HP1α on the promoter regions of RPLP0, TNFα, and HERVs in study individuals analyzed in Figure 6C. Represented values are Spearman Rank correlation coefficients followed by p-values calculated using two sided student t test. p<0.05...

PADI activity facilitates activation of HERVs in T cells. (A) ChIP with anti-HP1α antibodies was carried out with chromatin prepared from Jurkat cells either untreated or treated with PMA and ionophore (ionomycin). The relative enrichments of HP1α on the indicated LTRs were measured by qPCR. Data are presented relative to non-immune IgG. Changes in...

List of primers used in this study. (DOC)

Multiple Sclerosis (MS) is an autoimmune disease associated with abnormal expression of a subset of cytokines, resulting in inappropriate T-lymphocyte activation and uncontrolled immune response. A key issue in the field is the need to understand why these cytokines are transcriptionally activated in the patients. Here, we have examined several tra...

Cytosine methylation in mammals is important for epigenetic control of the transcriptome. Although altered methylation is frequently encountered in disease situations, particularly cancer, the relationship between genome-wide methylation and DNA structure is poorly understood. It is now evident that alternative DNA forms are functionally relevant i...

Epigenetic modifications, especially alteration in DNA methylation, are increasingly being recognized as a key factor in the pathogenesis of complex disorders, including atherosclerosis. However, there are limited data on the epigenetic changes in the coronary artery disease (CAD) patients. In the present study we evaluated the methylation status o...

Homocysteine is an independent risk factor for cardiovascular diseases. It is also known to be associated with a variety of complex disorders. While there are a large number of independent studies implicating homocysteine in isolated pathways, the mechanism of homocysteine induced adverse effects are not clear. Homocysteine-induced modulation of ge...

An elevated level of homocysteine is an independent risk factor for cardiovascular diseases and is associated with other complex disorders. Homocysteine levels can be elevated due to dietary and/or genetic factors. A majority of Indian population have a low level of vitamin B12 (presumably due to vegetarian diet)--a critical nutritional factor, def...