Intrinsic properties of Tcf1 and Tcf4 splice variants determine cell-type-specific Wnt/β-catenin target gene expression

Glucocorticoids are potent anti-inflammatory drugs; however, their molecular mode of action remains complex and elusive. They bind to the glucocorticoid receptor (GR), a nuclear receptor that controls gene expression in almost all tissues in a cell type-specific manner. While GR’s transcriptional targets mediate beneficial reactions in immune cells, they also harbor the potential of adverse metabolic effects in other cell types such as hepatocytes. Here, we have profiled nascent transcription upon glucocorticoid stimulation in LPS-activated primary murine macrophages using 4sU-seq. We compared our results to publicly available nascent transcriptomics data from murine liver and bioinformatically identified non-coding RNAs transcribed from intergenic GR binding sites in a tissue-specific fashion. These tissue-specific enhancer RNAs (eRNAs) correlate with target gene expression, reflecting cell type-specific glucocorticoid responses. We further associate GR-mediated eRNA expression with changes in H3K27 acetylation and BRD4 recruitment in inflammatory macrophages upon glucocorticoid treatment. In summary, we propose a common mechanism by which GR-bound enhancers regulate target gene expression by changes in histone acetylation, BRD4 recruitment and eRNA expression. We argue that local eRNAs are potential therapeutic targets downstream of GR signaling which may modulate glucocorticoid response in a cell type-specific way.

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DEBay: a computational tool for deconvolution of quantitative PCR data for estimation of cell type-specifc gene expression in a mixed population

10.1101/2020.04.10.035642 ◽

2020 ◽

Author(s):

Vimalathithan Devaraj ◽

Biplab Bose

Keyword(s):

Gene Expression ◽

Quantitative Pcr ◽

Target Gene ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Mixed Population ◽

Specific Gene ◽

Cell Type ◽

Computational Tool ◽

Cell Type Specific

AbstractThe expression of a gene is commonly estimated by quantitative PCR (qPCR) using RNA isolated from a large number of pooled cells. Such pooled samples often have subpopulations of cells with different levels of expression of the target gene. Estimation of gene expression from an ensemble of cells obscures the pattern of expression in different subpopulations. Physical separation of various subpopulations is a demanding task. We have developed a computational tool, Deconvolution of Ensemble through Bayes-approach (DEBay), to estimate cell type-specific gene expression from qPCR data of a mixed population. DEBay estimates Normalized Gene Expression Coefficient (NGEC), which is a relative measure of the expression of the target gene in each cell type in a population. NGEC has a direct algebraic correspondence with the normalized fold change in gene expression measured by qPCR. DEBay can deconvolute both time-dependent and -independent gene expression profiles. It uses the Bayesian method of model selection and parameter estimation. We have evaluated DEBay using synthetic and real experimental data. DEBay is implemented in Python. A GUI of DEBay and its source code are available for download at SourceForge (https://sourceforge.net/projects/debay).

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2049-P: The Chd4 Helicase of the Nucleosome Remodeling and Deacetylase Complex Modulates Pdx1 Target Gene Expression In Vitro

Diabetes ◽

10.2337/db20-2049-p ◽

2020 ◽

Vol 69 (Supplement 1) ◽

pp. 2049-P

Author(s):

REBECCA K. DAVIDSON ◽

NOLAN CASEY ◽

JASON SPAETH

Keyword(s):

Gene Expression ◽

Target Gene ◽

Nucleosome Remodeling ◽

Target Gene Expression

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Faculty Opinions recommendation of The kinase p38 alpha serves cell type-specific inflammatory functions in skin injury and coordinates pro- and anti-inflammatory gene expression.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1135937.593041 ◽

2008 ◽

Author(s):

Lionel Ivashkiv

Keyword(s):

Gene Expression ◽

Cell Type ◽

Skin Injury ◽

Inflammatory Gene Expression ◽

Inflammatory Gene ◽

Cell Type Specific ◽

Anti Inflammatory

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Faculty Opinions recommendation of BMP signaling induces cell-type-specific changes in gene expression programs of human keratinocytes and fibroblasts.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1927959.1482057 ◽

2010 ◽

Author(s):

Ralf Paus

Keyword(s):

Gene Expression ◽

Human Keratinocytes ◽

Bmp Signaling ◽

Cell Type ◽

Cell Type Specific

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An integrated analysis of cell-type specific gene expression reveals genes regulated by REVOLUTA and KANADI1 in the Arabidopsis shoot apical meristem

PLoS Genetics ◽

10.1371/journal.pgen.1008661 ◽

2020 ◽

Vol 16 (4) ◽

pp. e1008661 ◽

Cited By ~ 2

Author(s):

Hasthi Ram ◽

Sudeep Sahadevan ◽

Nittaya Gale ◽

Monica Pia Caggiano ◽

Xiulian Yu ◽

...

Keyword(s):

Gene Expression ◽

Shoot Apical Meristem ◽

Apical Meristem ◽

Integrated Analysis ◽

Specific Gene ◽

Cell Type ◽

Specific Gene Expression ◽

Cell Type Specific

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Cortical structural differences in major depressive disorder correlate with cell type-specific transcriptional signatures

Nature Communications ◽

10.1038/s41467-021-21943-5 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Jiao Li ◽

Jakob Seidlitz ◽

John Suckling ◽

Feiyang Fan ◽

Gong-Jun Ji ◽

...

Keyword(s):

Gene Expression ◽

Major Depressive Disorder ◽

Depressive Disorder ◽

Structural Changes ◽

Brain Regions ◽

Cell Type ◽

Major Depressive ◽

Structural Differences ◽

Neuroimaging Data ◽

Cell Type Specific

AbstractMajor depressive disorder (MDD) has been shown to be associated with structural abnormalities in a variety of spatially diverse brain regions. However, the correlation between brain structural changes in MDD and gene expression is unclear. Here, we examine the link between brain-wide gene expression and morphometric changes in individuals with MDD, using neuroimaging data from two independent cohorts and a publicly available transcriptomic dataset. Morphometric similarity network (MSN) analysis shows replicable cortical structural differences in individuals with MDD compared to control subjects. Using human brain gene expression data, we observe that the expression of MDD-associated genes spatially correlates with MSN differences. Analysis of cell type-specific signature genes suggests that microglia and neuronal specific transcriptional changes account for most of the observed correlation with MDD-specific MSN differences. Collectively, our findings link molecular and structural changes relevant for MDD.

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On the way toward regulatable expression systems in acetic acid bacteria: target gene expression and use cases

Applied Microbiology and Biotechnology ◽

10.1007/s00253-021-11269-z ◽

2021 ◽

Author(s):

Philipp Moritz Fricke ◽

Angelika Klemm ◽

Michael Bott ◽

Tino Polen

Keyword(s):

Gene Expression ◽

Acetic Acid ◽

Literature Search ◽

Target Gene ◽

Target Genes ◽

Recombinant Dna ◽

Acetic Acid Bacteria ◽

Homoserine Lactone ◽

Expression Systems ◽

Target Gene Expression

Abstract Acetic acid bacteria (AAB) are valuable biocatalysts for which there is growing interest in understanding their basics including physiology and biochemistry. This is accompanied by growing demands for metabolic engineering of AAB to take advantage of their properties and to improve their biomanufacturing efficiencies. Controlled expression of target genes is key to fundamental and applied microbiological research. In order to get an overview of expression systems and their applications in AAB, we carried out a comprehensive literature search using the Web of Science Core Collection database. The Acetobacteraceae family currently comprises 49 genera. We found overall 6097 publications related to one or more AAB genera since 1973, when the first successful recombinant DNA experiments in Escherichia coli have been published. The use of plasmids in AAB began in 1985 and till today was reported for only nine out of the 49 AAB genera currently described. We found at least five major expression plasmid lineages and a multitude of further expression plasmids, almost all enabling only constitutive target gene expression. Only recently, two regulatable expression systems became available for AAB, an N-acyl homoserine lactone (AHL)-inducible system for Komagataeibacter rhaeticus and an l-arabinose-inducible system for Gluconobacter oxydans. Thus, after 35 years of constitutive target gene expression in AAB, we now have the first regulatable expression systems for AAB in hand and further regulatable expression systems for AAB can be expected. Key points • Literature search revealed developments and usage of expression systems in AAB. • Only recently 2 regulatable plasmid systems became available for only 2 AAB genera. • Further regulatable expression systems for AAB are in sight.

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Histone modifications form a cell-type-specific chromosomal bar code that persists through the cell cycle

Scientific Reports ◽

10.1038/s41598-021-82539-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

John A. Halsall ◽

Simon Andrews ◽

Felix Krueger ◽

Charlotte E. Rutledge ◽

Gabriella Ficz ◽

...

Keyword(s):

Gene Expression ◽

Cell Cycle ◽

Histone Modifications ◽

Expression Patterns ◽

Cell Types ◽

Cell Type ◽

Bar Code ◽

Genes Encoding ◽

Cell Type Specific ◽

Rolling Windows

AbstractChromatin configuration influences gene expression in eukaryotes at multiple levels, from individual nucleosomes to chromatin domains several Mb long. Post-translational modifications (PTM) of core histones seem to be involved in chromatin structural transitions, but how remains unclear. To explore this, we used ChIP-seq and two cell types, HeLa and lymphoblastoid (LCL), to define how changes in chromatin packaging through the cell cycle influence the distributions of three transcription-associated histone modifications, H3K9ac, H3K4me3 and H3K27me3. We show that chromosome regions (bands) of 10–50 Mb, detectable by immunofluorescence microscopy of metaphase (M) chromosomes, are also present in G1 and G2. They comprise 1–5 Mb sub-bands that differ between HeLa and LCL but remain consistent through the cell cycle. The same sub-bands are defined by H3K9ac and H3K4me3, while H3K27me3 spreads more widely. We found little change between cell cycle phases, whether compared by 5 Kb rolling windows or when analysis was restricted to functional elements such as transcription start sites and topologically associating domains. Only a small number of genes showed cell-cycle related changes: at genes encoding proteins involved in mitosis, H3K9 became highly acetylated in G2M, possibly because of ongoing transcription. In conclusion, modified histone isoforms H3K9ac, H3K4me3 and H3K27me3 exhibit a characteristic genomic distribution at resolutions of 1 Mb and below that differs between HeLa and lymphoblastoid cells but remains remarkably consistent through the cell cycle. We suggest that this cell-type-specific chromosomal bar-code is part of a homeostatic mechanism by which cells retain their characteristic gene expression patterns, and hence their identity, through multiple mitoses.

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