Disruption of ESR1 alters the expression of genes regulating hepatic lipid and carbohydrate metabolism in male rats

Khristi, Vincentaben; Ratri, Anamika; Ghosh, Subhra; Pathak, Devansh; Borosha, Shaon; Dai, Eddie; Roy, Richita; Chakravarthi, V. Praveen; Wolfe, Michael W.; Rumi, M.A. Karim

doi:10.1016/j.mce.2019.04.005

Cited by 35 publications

(22 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Quantitative realtime PCR (qPCR) was performed using Power SYBR Green Master Mix (ThermoFisher Scientific) and ran on a 7500 real-time PCR system (Applied Biosystems). qPCR results were normalized to Rn18S expression and calculated by the comparative ΔΔCT method (Chakravarthi et al, 2020;Khristi et al, 2018;Khristi et al, 2019). A list of qPCR primer sequences used in this study is shown in Table 1 (http://pga.mgh.harvard.edu/primerbank/).…”

Section: Rna Extraction Cdna Preparation and Rt-qpcrmentioning

confidence: 99%

DOT1L methyltransferase regulates the calcium influx in erythroid progenitor cells in response to erythropoietin

Feng

Borosha

Ratri

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

Erythropoietin (EPO) signaling plays a vital role in erythropoiesis by regulating proliferation and lineage-specific differentiation of hematopoietic progenitor cells. An important downstream response of EPO signaling is calcium influx, which is regulated by transient receptor potential channel (TRPC) proteins, particularly TRPC2 and TRPC6. While EPO induces Ca2+influx through TRPC2, TRPC6 inhibits the function of TRPC2. Thus, interactions between TRPC2 and TRPC6 regulate the rate of Ca2+influx in EPO-induced erythropoiesis. In this study, we observed that the expression of TRPC6 in c-KIT positive erythroid progenitor cells is regulated by DOT1L. DOT1L is a methyltransferase that plays an important role in many biological processes during embryonic development, including early erythropoiesis. We previously reported that Dot1L knockout (Dot1L-KO) hematopoietic progenitors in the yolk sac failed to develop properly, which resulted in lethal anemia. In this study, we have detected a marked downregulation of Trpc6 gene expression in Dot1L-KO progenitor cells in the yolk sac compared to wildtype. However, the expression of Trpc2, the positive regulator of Ca2+influx, remained unchanged. The promoter and the proximal region of the Trpc6 gene loci exhibited an enrichment of H3K79 methylation, which is mediated solely by DOT1L. As the loss of DOT1L affects the expression of TRPC6, which inhibits Ca2+influx by TRPC2, Dot1L-KO progenitor cells in the yolk sac exhibit accelerated and sustained high levels of Ca2+influx. Such heightened Ca2+ levels might have detrimental effects on the development of hematopoietic progenitor cells in response to erythropoietin.

show abstract

Section: Rna Extraction Cdna Preparation and Rt-qpcrmentioning

confidence: 99%

DOT1L methyltransferase regulates the calcium influx in erythroid progenitor cells in response to erythropoietin

Feng

Borosha

Ratri

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…In both males and females, the estrogen receptor (ER), ESR1, is the main receptor in the liver and mediates the liver's response to estrogen. 47 As an important sex hormone, estrogen functions in various processes such as cell metabolism, cell differentiation, and tissue development. 48 Villa et al proved that the transcript status of ER in patients with HCC has a novel value in prognosis.…”

mentioning

confidence: 99%

Using Integrated Bioinformatics Analysis to Identify Abnormally Methylated Differentially Expressed Genes in Hepatocellular Carcinoma

Chen¹,

Yan²,

Feng³

et al. 2021

IJGM

View full text Add to dashboard Cite

Objective For the identification of abnormally methylated differentially expressed genes (MDEGs) in hepatocellular carcinoma (HCC), this study integrated four microarray datasets to investigate the fundamental mechanisms of tumorigenesis. Methods We obtained the expression (GSE76427, GSE57957) and methylation (GSE89852, GSE54503) profiles from Gene Expression Omnibus (GEO). The abnormally MDEGs were identified by using R software. We used the clusterProfiler package for the functional and pathway enrichment analysis. The String database was used to build the protein–protein interaction (PPI) network and visualize it in Cytoscape. MCODE was employed in the module analysis. Additionally, Gene Expression Profiling Interactive Analysis (GEPIA) and The Cancer Genome Atlas (TCGA) were employed to validate results. Lastly, we used cBioPortal software to examine the hub genetic alterations. Results We identified 162 hypermethylated, down-regulated genes and 190 hypomethylated, up-regulated genes. Up-regulated genes with low methylation were enriched in biological processes, such as keratinocyte proliferation, and calcium homeostasis. Pathway analysis was enriched in the AMPK and PI3K-Akt signaling pathways. The PPI network identified PTK2, VWF, and ITGA2 as hypomethylated, high-expressing hub genes. Down-regulated genes with high methylation were related to responses to peptide hormones and estradiol, multi-multicellular organism process. Pathway analysis indicated enrichment in camp, oxytocin signaling pathways. The PPI network identified CFTR, ESR1, and CXCL12 as hypermethylated, low-expressing hub genes. Upon verification in TCGA databases, we found that the expression and methylation statuses of the hub genes changed significantly, and it was consistent with our results. Conclusion The novel abnormally MDEGs and pathways in HCC were identified. These results helped us further understand the molecular mechanisms underlying HCC invasion, metastasis, and development. Hub genes can serve as biomarkers for an accurate diagnosis and treatment of HCC, and PTK2, VWF, ITGA2, CFTR, ESR1, and CXCL12 are included.

show abstract

“…• ESR1 serves as a key TF in regulating CYP3A4, a drug metabolizing enzymes in liver 61 , and its disruption in male rats leads to the change in expression of genes regulating hepatic lipid and carbohydrate metabolism 62 . Moreover, knockout of ESR1 alters the development of stress-related responses as well as psychomotor responses in male and female mice 63 .…”

Section: Communication Efficiency and Fault-tolerance This Experimenmentioning

confidence: 99%

Motifs enable communication efficiency and fault-tolerance in transcriptional networks

Roy

Ghosh

Barua

et al. 2020

Sci Rep

View full text Add to dashboard Cite

Analysis of the topology of transcriptional regulatory networks (TRNs) is an effective way to study the regulatory interactions between the transcription factors (TFs) and the target genes. TRNs are characterized by the abundance of motifs such as feed forward loops (FFLs), which contribute to their structural and functional properties. In this paper, we focus on the role of motifs (specifically, FFLs) in signal propagation in TRNs and the organization of the TRN topology with FFLs as building blocks. To this end, we classify nodes participating in FFLs (termed motif central nodes) into three distinct roles (namely, roles A, B and C), and contrast them with TRN nodes having high connectivity on the basis of their potential for information dissemination, using metrics such as network efficiency, path enumeration, epidemic models and standard graph centrality measures. We also present the notion of a three tier architecture and how it can help study the structural properties of TRN based on connectivity and clustering tendency of motif central nodes. Finally, we motivate the potential implication of the structural properties of motif centrality in design of efficient protocols of information routing in communication networks as well as their functional properties in global regulation and stress response to study specific disease conditions and identification of drug targets.

show abstract

Disruption of ESR1 alters the expression of genes regulating hepatic lipid and carbohydrate metabolism in male rats

Cited by 35 publications

References 67 publications

DOT1L methyltransferase regulates the calcium influx in erythroid progenitor cells in response to erythropoietin

DOT1L methyltransferase regulates the calcium influx in erythroid progenitor cells in response to erythropoietin

Using Integrated Bioinformatics Analysis to Identify Abnormally Methylated Differentially Expressed Genes in Hepatocellular Carcinoma

Motifs enable communication efficiency and fault-tolerance in transcriptional networks

Contact Info

Product

Resources

About