The authors regret typing errors on page 132 in the DNA sequence of mHsp-2686-RT-RP primer in the second sentence of the subsection entitled “Extraction of RNA and real-time PCR” under the Materials and Methods section of the article. The sentence should be read as follows: Real-time PCR was carried out using the DyNAmo™ HS SYBR® Green qPCR kit (Finnzymes, USA) and mHspa1a gene-specific primers (forward, mHsp-2406-RT-FP: 5′-TGCCCCGCTGATGTGATTTG-3′ and reverse, mHsp-2686-RT-RP: 5′-CACCAACCTGGAAACAAGTCCTAC-3′). The authors would like to apologize for any inconvenience caused. © 2019

Nitish R. Mahapatra

Department Of Biotechnology

Binu K. Sasi

erratum

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IIT Madras is a public technical and research university located in Chennai, Tamil Nadu. Founded in 1959, it is recognised as an Institute of National Importance.

IIT Madras has been ranked as the top engineering institute in India for four years in a row by the National Institutional Ranking Framework of the MHRD

It currently offers undergraduate, postgraduate and research degrees across 16 disciplines in Engineering, Sciences, Humanities and Management. About 596 faculty belonging to science and engineering departments and centres of the Institute are engaged in teaching, research and industrial consultancy.

IIT Madras

Journal of Molecular Biology

Monoamine oxidase B (MAO-B), a flavoenzyme located in the outer mitochondrial membrane, is involved in the catabolism of monoamines. Altered levels of MAO-B are associated with cardiovascular/neuronal diseases. However, molecular mechanisms of MAO-B gene regulation are partially understood. We undertook a systematic analysis of the MAO-B gene to identify the key transcriptional/post-transcriptional regulatory molecules. Expression of MAO-B promoter–reporter constructs in cultured cells identified the − 144/+25-bp domain as the core promoter region. Stringent in silico analysis of this core promoter predicted binding sites for several transcription factors. Over-expression/down-regulation of transcription factors Sp1/Egr1/CREB increased/decreased the MAO-B promoter–reporter activity and endogenous MAO-B protein level. Electrophoretic mobility shift assays and ChIP assays provided evidence for interactions of Sp1/Egr1/CREB with the MAO-B promoter. MAOB transcript level also positively correlated with the transcript level of Sp1/Egr1/CREB in various human tissue samples. Computational predictions using multiple algorithms coupled with systematic functional analysis revealed direct interactions of the microRNAs miR-1224 and miR-300 with MAO-B 3′-UTR. Dopamine dose-dependently enhanced MAO-B transcript and protein levels via increased binding of CREB to MAO-B promoter and reduced miR-1224/miR-300 levels. 8-Bromo-cAMP and forskolin augmented MAO-B expression, whereas inhibition of PKA diminished the gene expression suggesting involvement of cAMP-PKA axis. Interestingly, Sp1/Egr1/CREB/miR-1224 levels correlate with MAO-B expression in rodent models of hypertension/MPTP-induced neurodegeneration, indicating their roles in governing MAO-B gene expression in these disease states. Taken together, this study elucidates the previously unknown roles of the transcription factors Sp1/Egr1/CREB and microRNAs miR-1224/miR-300 in regulating MAO-B gene expression under basal/disease states involving dysregulated catecholamine levels. © 2019 Elsevier Ltd

Regulation of Monoamine Oxidase B Gene Expression: Key Roles for Transcription Factors Sp1, Egr1 and CREB, and microRNAs miR-300 and miR-1224

The acidic glycoprotein chromogranin A (CHGA) is co-stored/co-secreted with catecholamines and crucial for secretory vesicle biogenesis in neuronal/neuroendocrine cells. CHGA is dysregulated in several cardiovascular diseases, but the underlying mechanisms are not well established. Here, we sought to identify common polymorphisms in the CHGA promoter and to explore the mechanistic basis of their plausible contribution to regulating CHGA protein levels in circulation. Resequencing of the CHGA promoter in an Indian population (n=769) yielded nine single-nucleotide polymorphisms (SNPs): G-1106A, A-1018T, T-1014C, T-988G,G-513A,G-462A, T-415C, C-89A, and C-57T. Linkage disequilibrium (LD) analysis indicated strong LD among SNPs at the -1014, -988, -462, and -89 bp positions and between the -1018 and -57 bp positions. Haplotype analysis predicted five major promoter haplotypes that displayed differential promoter activities in neuronal cells; specifically, haplotype 2 (containing variant T alleles at -1018 and -57 bp) exhibited the highest promoter activity. Systematic computational and experimental analyses revealed that transcription factor c-Rel has a role in activating the CHGA promoter haplotype 2 under basal and pathophysiological conditions(viz. inflammation and hypoxia). Consistent with the higher in vitro CHGA promoter activity of haplotype 2, individuals carrying this haplotype had higher plasma CHGA levels,plasma glucose levels, diastolic blood pressure, and body mass index. In conclusion, these results suggest a functional role of the CHGA promoter haplotype 2 (occurring in a large proportionof the world population) in enhancing CHGA expression in haplotype 2 carriers who may be at higher risk for cardiovascular/metabolic disorders. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Journal of Biological Chemistry

A haplotype variant of the human chromogranin A gene (CHGA) promoter increases CHGA expression and the risk for cardiometabolic disorders

Abstract Transcription factor Snail mediates epithelial to mesenchymal transitions (EMT) by coordinate repression of epithelial markers, facilitating mass cell movement during germ layer formation. Aberrant reprogramming in its signaling pathways causes metastatic cancer. Snail's involvement in "fate-changing" decisions is however not understood. Cripto-1 shares a common temporal expression pattern with Snail during development. While Cripto-1 is required for mammary morphogenesis and hematopoietic stem cell renewal, its unregulated expression causes metastatic cancers. Therefore, we suspected that Snail regulates the expression of Cripto-1 controlling decisions such as motility, transformation and differentiation. We demonstrate that Snail represses Cripto-1 gene by direct transcriptional interaction and propose a novel mechanism by which it co-ordinately regulates cell fate decisions during development and could be causal of cancers. © 2015 Federation of European Biochemical Societies.

FEBS Letters

Snail-mediated Cripto-1 repression regulates the cell cycle and epithelial-mesenchymal transition-related gene expression

Monoamine oxidase A (MAOA) plays important roles in the pathogenesis of several neurological and cardiovascular disorders. The mechanism of transcriptional regulation of MAOA under basal and pathological conditions, however, remains incompletely understood. Here, we report systematic identification and characterization of cis elements and transcription factors that govern the expression of MAOA gene. Extensive computational analysis of MAOA promoter, followed by 5′-promoter deletion/reporter assays, revealed that the -71/-40 bp domain was sufficient for its basal transcription. Gel-shift and chromatin immunoprecipitation assays provided evidence of interactions of the transcription factors GATA-binding protein 2 (GATA2), Sp1 and TATA-binding protein (TBP) with this proximal promoter region. Consistently, over-expression of GATA2, Sp1 and TBP augmented MAOA promoter activity in a coordinated manner. In corroboration, siRNA-mediated down-regulation of GATA2/Sp1/TBP repressed the endogenous MAOA expression as well as transfected MAOA promoter activity. Tumor necrosis factor-α and forskolin activated MAOA transcription that was reversed by Sp1 siRNA; in support, tumor necrosis factor-α- and forskolin-induced activities were enhanced by ectopic over-expression of Sp1. On the other hand, MAOA transcription was diminished upon exposure of neuroblasts or cardiac myoblasts to ischemia-like conditions because of reduced binding of GATA2/Sp1/TBP with MAOA promoter. In conclusion, this study revealed previously unknown roles of GATA2, Sp1 and TBP in modulating MAOA expression under basal as well as pathophysiological conditions such as inflammation and ischemia, thus providing new insights into the molecular basis of aberrant MAOA expression in neuronal/cardiovascular disease states. © 2015 International Society for Neurochemistry.

Journal of Neurochemistry

Molecular mechanism of monoamine oxidase A gene regulation under inflammation and ischemia-like conditions: Key roles of the transcription factors GATA2, Sp1 and TBP

Corrigendum to “Coordinated Transcriptional Regulation of Hspa1a Gene by Multiple Transcription Factors: Crucial Roles for HSF-1, NF-Y, NF-κB, and CREB” (Coordinated Transcriptional Regulation of Hspa1a Gene by Multiple Transcription Factors: Crucial Roles for HSF-1, NF-Y, NF-κB, and CREB (2014) 426(1) (116–135), (S0022283613005779), (10.1016/j.jmb.2013.09.008))

Journal	Journal of Molecular Biology
Publisher	Academic Press
ISSN	00222836
Open Access	Yes