Histone Chaperones Regulate Mammalian Gene Expression

Histone chaperones are fundamental molecules that aid in the synthesis, translocation, and exchange of histones across the barrier of cytoplasm to nucleus. Regulation in repair, replication, and nucleosome assembly constitute the widely associated functions of histone chaperones. Recently, they have been associated with transcriptional regulation. Different stages of mammalian development have been correlated to the expression of histone chaperones. From oocyte and sperm till the formation and development of zygote, different histone chaperones demonstrated distinct regulatory roles. Efficient models of studying mammalian development include differentiation of embryonic stem cells (ESCs) to different lineages. Both in vitro and in vivo differentiation of mammalian cells exhibit regulation by different subtypes of histone chaperones. Due to the ethical issues concerning the use of embryos for the derivation of ESCs, induced pluripotent stem cells (iPSCs) were derived from pre-existing differentiated cells by a phenomenon called cellular reprogramming. Cellular reprogramming is characterized by erasure of pre-existing epigenetic signature to a new modulated epigenome. Histone chaperones serve as either facilitator or barrier to reprogramming. Here, we will discuss how histone chaperones could regulate the gene expression pattern by regulating epigenetic modification during the complex process of mammalian development and reprogramming

Regional analysis of sanitation performance in India

India bears a disproportionate burden of open defecation in spite of investing more and more funds and ushering in several institutional efforts including the Swachh Bharat Mission in the recent past. A large share of rural households still lack basic sanitation facilities in India and members practice open defecation. Thia study endeavours to examine the existing anomaly between meagre sanitation productivity and enhanced resource allocation in rural sanitation in India. The study attempts to develop an instrument to monitor the differential regional performances across India

Protocol for isolation of mouse pre-implantation embryos for gene expression analysis

Summary: Visualizing and quantifying the numerous factors that regulate murine pre-implantation embryonic development is technically challenging. Here, we present a protocol for the isolation of pre-implantation embryos at multiple stages of embryonic development to study gene expression. We describe steps for isolating RNA and cDNA synthesis from a small number of embryos. We then detail an immunofluorescence assay for the detection and localization of protein of interest by confocal microscopy in the pre-implantation embryos.For complete details on the use and execution of this protocol, please refer to Varghese et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics

Successful hybrid management of hypertensive patent ductus arteriosus with unilateral absence of the right pulmonary artery – A case report

Unilateral absence of pulmonary artery (UAPA) can be either isolated or associated with other congenital cardiac defects. It is a rare congenital lesion with a diverse clinical presentation. We present a case of absent right pulmonary artery and large patent ductus arteriosus (PDA) with severe unilateral pulmonary hypertension. We describe our strategy of staged ductus arteriosus closure in this patient and successful outcome on long term follow up

PTEN-negative endometrial cancer cells protect their genome through enhanced DDB2 expression associated with augmented nucleotide excision repair

Abstract Background Endometrial cancer (EC) arises from uterine endometrium tissue and is the most prevalent cancer of the female reproductive tract in developed countries. It has been predicted that the global prevalence of EC will increase in part because of its positive association with economic growth and lifestyle. The majority of EC presented with endometrioid histology and mutations in the tumor suppressor gene PTEN, resulting in its loss of function. PTEN negatively regulates the PI3K/Akt/mTOR axis of cell proliferation and thus serves as a tumorigenesis gatekeeper. Through its chromatin functions, PTEN is also implicated in genome maintenance procedures. However, our comprehension of how DNA repair occurs in the absence of PTEN function in EC is inadequate. Methods We utilized The Cancer Genome Atlas (TCGA) data analysis to establish a correlation between PTEN and DNA damage response genes in EC, followed by a series of cellular and biochemical assays to elucidate a molecular mechanism utilizing the AN3CA cell line model for EC. Results The TCGA analyses demonstrated an inverse correlation between the expression of the damage sensor protein of nucleotide excision repair (NER), DDB2, and PTEN in EC. The transcriptional activation of DDB2 is mediated by the recruitment of active RNA polymerase II to the DDB2 promoter in the PTEN-null EC cells, revealing a correlation between increased DDB2 expression and augmented NER activity in the absence of PTEN. Conclusion Our study indicated a causal relationship between NER and EC that may be exploited in disease management

Enhanced expression of histone chaperone APLF associate with breast cancer

Abstract DNA damage-specific histone chaperone Aprataxin PNK-like factor (APLF) regulates mesenchymal-to-epithelial transition (MET) during cellular reprogramming. We investigated the role of APLF in epithelial-to-mesenchymal transition (EMT) linked to breast cancer invasiveness and metastasis. Here, we show that a significant manifestation of APLF is present in tumor sections of patients with invasive ductal carcinoma when compared to their normal adjacent tissues. APLF was significantly induced in triple negative breast cancer (TNBC) cells, MDAMB-231, in comparison to invasive MCF7 or normal MCF10A breast cells and supported by studies on invasive breast carcinoma in The Cancer Genome Atlas (TCGA). Functionally, APLF downregulation inhibited proliferative capacity, altered cell cycle behavior, induced apoptosis and impaired DNA repair ability of MDAMB-231 cells. Reduction in APLF level impeded invasive, migratory, tumorigenic and metastatic potential of TNBC cells with loss in expression of genes associated with EMT while upregulation of MET-specific gene E-cadherin (CDH1). So, here we provided novel evidence for enrichment of APLF in breast tumors, which could regulate metastasis-associated EMT in invasive breast cancer. We anticipate that APLF could be exploited as a biomarker for breast tumors and additionally could be targeted in sensitizing cancer cells towards DNA damaging agents

Additional file 3: of Enhanced expression of histone chaperone APLF associate with breast cancer

Expression of EMT associated genes related to Figure S7B. (XLSX 10 kb