Alla A. Sigova

Antisense Oligonucleotides Targeting an LDLR Regulatory RNA Increase LDLR Expression and Reduce LDL-cholesterol in Vivo

Keerthana Gnanapradeepan, Salomé Manska, Brian Schwartz, Gabriel Golczer et autres

Abstract Regulatory RNAs (regRNAs) are non-coding RNAs expressed from promoters and enhancers that modulate gene transcription. Targeting regRNAs with antisense oligonucleotides (ASOs) can increase transcription and presents a potential therapeutic strategy to restore expression in haploinsufficient diseases. This approach requires high-quality regRNA …

Profiling and Targeting of Regulatory RNAs to Upregulate Gene Expression

Brynn N. Akerberg, Bryan J. Matthews, Yuting Liu, Cécile Mathieu et autres

Abstract Transcription of long noncoding RNAs (lncRNAs), including enhancer RNAs (eRNAs) and promoter-associated RNAs (paRNAs), collectively termed regulatory RNAs (regRNAs), is a hallmark of active gene expression, yet it remains unknown whether regRNAs can be targeted to selectively enhance transcription in cis …

Author Correction: Transcriptional characterization of iPSC-derived microglia as a model for therapeutic development in neurodegeneration

Gokul Ramaswami, Yeliz Yuva-Aydemir, Brynn N. Akerberg, Bryan J. Matthews et autres

“G.R. performed computational analyses and wrote the manuscript draft. Y.Y., B.A., B.M., J.W., and A.A.A. performed experiments. G.G., J.H., and Y.L. performed computational analyses. D.H., L.C.B., S.J.E., I.G., A.S., A.A.S., R.T.F., Y.L., and D.B. supervised the experiments and computational analyses. All authors …

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Transcriptional characterization of iPSC-derived microglia as a model for therapeutic development in neurodegeneration

Gokul Ramaswami, Yeliz Yuva-Aydemir, Brynn N. Akerberg, Bryan J. Matthews et autres

Microglia are the resident immune cells in the brain that play a key role in driving neuroinflammation, a hallmark of neurodegenerative disorders. Inducible microglia-like cells have been developed as an in vitro platform for molecular and therapeutic hypothesis generation and testing. However, …

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JMnorm: a novel joint multi-feature normalization method for integrative and comparative epigenomics

Guanjue Xiang, Yuchun Guo, David A. Bumcrot, Alla A. Sigova

Combinatorial patterns of epigenetic features reflect transcriptional states and functions of genomic regions. While many epigenetic features have correlated relationships, most existing data normalization approaches analyze each feature independently. Such strategies may distort relationships between functionally correlated epigenetic features and hinder biological …

Government statement as a genre of political discourse(on the example of the speeches of the German chancellors A. Merkel and O. Scholz)

M. A. Yelizaryeva, Elena A. Bykova, Alla A. Sigova

The article examines the genre of a government statement in Germany in terms of political content and linguopragmatic specificities. It should be noted that this genre can be described as orientational-ritual, which is characterized by informing and integration strategies, as well as …

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JMnorm: a novel Joint Multi-feature normalization method for integrative and comparative epigenomics

Guanjue Xiang, Yuchun Guo, David A. Bumcrot, Alla A. Sigova

ABSTRACT Combinatorial patterns of epigenetic features reflect transcriptional states and functions of genomic regions. While many epigenetic features have correlated relationships, most existing data normalization approaches analyze each feature independently. Such strategies may distort relationships between functionally correlated epigenetic features and hinder …

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Transcriptional characterization of iPSC-derived microglia as a model for therapeutic development in neurodegeneration

Gokul Ramaswami, Yeliz Yuva-Aydemir, Brynn N. Akerberg, Bryan J. Matthews et autres

Abstract Background Microglia are the resident immune cells in the brain that play a key role in driving neuroinflammation, a hallmark of neurodegenerative disorders. Inducible microglia-like cells have been developed as an in vitro platform for molecular and therapeutic hypothesis generation and …

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Discovery and Targeting of the Signaling Controls of PNPLA3 to Effectively Reduce Transcription, Expression, and Function in Pre-Clinical NAFLD/NASH Settings

Brian E. Schwartz, Vaishnavi Rajagopal, Cynthia J. Smith, Evan Cohick et autres

Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are emerging worldwide epidemics, projected to become the leading cause of liver transplants. The strongest genetic risk factor for NAFLD/NASH susceptibility and progression is a single-nucleotide polymorphism (SNP) in the patatin-like phospholipase domain-containing …

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YY1 Is a Structural Regulator of Enhancer-Promoter Loops

Abraham S. Weintraub, Charles H. Li, Alicia Viridiana Zamudio, Alla A. Sigova et autres

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YY1 Is a Structural Regulator of Enhancer-Promoter Loops

Alla A. Sigova, Nancy M. Hannett, Daniel S. Day, Brian J. Abraham et autres

DIGIT Is a Conserved Long Noncoding RNA that Regulates GSC Expression to Control Definitive Endoderm Differentiation of Embryonic Stem Cells

Kaveh Daneshvar, Joshua V. Pondick, Byeong–Moo Kim, Chan Zhou et autres

Long noncoding RNAs (lncRNAs) exhibit diverse functions, including regulation of development. Here, we combine genome-wide mapping of SMAD3 occupancy with expression analysis to identify lncRNAs induced by activin signaling during endoderm differentiation of human embryonic stem cells (hESCs). We find that DIGIT …

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