A mouse tissue transcription factor atlas

Zhou, Quan; Liu, Mingwei; Xia, Xia; Gong, Tongqing; Feng, Jinwen; Liu, Wanlin; Liu, Yang; Zhen, Bei; Wang, Yi; Ding, Chen; Qin, Jun

doi:10.1038/ncomms15089

Cited by 98 publications

(98 citation statements)

References 64 publications

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“…To investigate the biological roles of the tissue-specific versus the globally expressed proteins, we performed a gene ontology (GO) enrichment analysis across the proteinspecific tissue distributions, and found that globally expressed proteins are enriched for mitochondrial proteins involved in oxidative phosphorylation, whereas transcription factors 27 are generally tissue-specific proteins ( Figure 5J). These findings are consistent with the fact that cellular housekeeping functions such as ATP production by oxidative phosphorylation is generic to all cell types, whereas tissue specificity is facilitated by temporal and spatial gene expression patterns, which are driven by transcription factors 28 .…”

Section: Quantitative Rat Organ Protein Atlas By Tmt and Dia-lfqsupporting

confidence: 86%

A Compact Quadrupole-Orbitrap Mass Spectrometer with FAIMS Interface Improves Proteome Coverage in Short LC Gradients

Bekker-Jensen

Martinez

Steigerwald

et al. 2019

Preprint

132

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State-of-the-art proteomics-grade mass spectrometers can measure peptide precursors and their fragments with ppm mass accuracy at sequencing speeds of tens of peptides per second with attomolar sensitivity. Here we describe a compact and robust quadrupole-orbitrap mass spectrometer equipped with a front-end High Field Asymmetric Waveform Ion Mobility Spectrometry (FAIMS) Interface. The performance of the Orbitrap Exploris 480 mass spectrometer is evaluated in data-dependent acquisition (DDA) and data-independent acquisition (DIA) modes in combination with FAIMS. We demonstrate that different compensation voltages (CVs) for FAIMS are optimal for DDA and DIA, respectively. Combining DIA with FAIMS using single CVs, the instrument surpasses 2500 unique peptides identified per minute. This enables quantification of >5000 proteins with short online LC gradients delivered by the Evosep One LC system allowing acquisition of 60 samples per day. The raw sensitivity of the instrument is evaluated by analyzing 5 ng of a HeLa digest from which >1000 proteins were reproducibly identified with 5 minute LC gradients using DIA-FAIMS. To demonstrate the versatility of the instrument we recorded an organ-wide map of proteome expression across 12 rat tissues quantified by tandem mass tags and label-free quantification using DIA with FAIMS to a depth of >10,000 proteins. The authors would like to thank Stoyan Stoychev and Justin Jordaan for great help and input for optimizing our phospho-enrichment workflow and establishing automated platform for sample preparation. We would also like to thank Nicolai Bache for help and input on the chromatographic methods as well as Anna Secher for providing rat tissues and all members of the Olsen Group for critical input on the manuscript.

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Section: Quantitative Rat Organ Protein Atlas By Tmt and Dia-lfqsupporting

confidence: 86%

A Compact Quadrupole-Orbitrap Mass Spectrometer with FAIMS Interface Improves Proteome Coverage in Short LC Gradients

Bekker-Jensen

Martinez

Steigerwald

et al. 2019

Preprint

132

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“…Although several miRNAs share the promoter of the host gene for their transcription, many might have separate promoters in the intronic region and may be transcribed independently of the host gene (24). Because ALR does not appear to have transcriptional activity (28), it may not directly influence the miRNA expression despite its presence in the nucleus. However, it is likely that ALR may associate with transcription factors and act as a coactivator or -repressor.…”

Section: Discussionmentioning

confidence: 99%

“…Although present in the nucleus, ALR does not seem to possess DNA-binding sequence (28), and thus unlikely to directly modulate gene expression including that of miRNAs. Because ALR depletion increases oxidative stress both in vivo and in vitro (5), ALR flox/flox hepatocytes were exposed to oxidative stress by H 2 O 2 or transfected with Adeno-Cre (Cell Biolabs).…”

Section: Alr Depletion From Hepatocytes Reduces Ppara Acox1 and Pmp70mentioning

confidence: 99%

Augmenter of liver regeneration protein deficiency promotes hepatic steatosis by inducing oxidative stress and microRNA‐540 expression

et al. 2018

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Levels of augmenter of liver regeneration (ALR), a multifunctional protein, are reduced in steatohepatitis. ALR depletion from ALRflox/flox/Alb‐Cre [ALR‐L‐knockout (KO)] mouse causes robust steatosis and apoptosis of hepatocytes, and pericellular fibrosis between 1 and 2 wk postbirth. Steatosis regresses by 4 wk upon reappearance of ALR‐expressing hepatocytes. We investigated mechanisms of ALR depletion‐induced steatosis. ALR‐L‐KO mice (1‐, 2‐, and 4 wk old) and Adeno‐Cre‐transfected ALRflox/flox hepatocytes were used for in vivo and in vitro studies. ALR depletion from hepatocytes in vivo downregulated peroxisome proliferator‐activated receptor (PPAR)‐α, carnitine palmitoyl transferase I (CPTl)a, peroxisomal membrane protein 70 (PMP70) (modest down‐regulation), and acyl‐CoA oxidase 1 (ACOX1). The markedly up‐regulated (20X) novel microRNA‐540 (miR‐540) was identified to target PPARα, PMP70, ACOX1, and CPT1a. ALR depletion from primary hepatocytes increased oxidative stress, miR‐540 expression, and steatosis and down‐regulated PPARα, ACOX1, PMP70, and CPT1a expression. Anti‐miR‐540 mitigated ALR depletion‐induced steatosis and prevented loss of PPARα, ACOX1, PMP70, and CPT1a expression. Antioxidant N‐acetylcysteine and recombinant ALR (rALR) both inhibited ALR depletion‐induced miR‐540 expression and lipid accumulation in hepatocytes. Finally, treatment of ALR‐L‐KO mice with rALR between 1 and 2 wk prevented miR‐540 expression, and arrested steatosis and fibrosis. We conclude that ALR deficiency‐mediated oxidative stress induces generation of miR‐540, which promotes steatosis by dysregulating peroxisomal and mitochondrial lipid homeostasis.—Kumar, S., Rani, R., Karns, R., Gandhi, C. R. Augmenter of liver regeneration protein deficiency promotes hepatic steatosis by inducing oxidative stress and microRNA‐540 expression. FASEB J. 33, 3825–3840 (2019). http://www.fasebj.org

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“…In the mammalian genome, there are approximately 1500 transcription factors (TFs) (Zhou et al 2017;Vaquerizas et al 2009), which bind to specific DNA sequences, within cis-regulatory modules (CRMs), to control gene expression and regulate almost every aspect of life. Many are used repeatedly, and in a variety of combinations, to regulate distinct developmental and homeostatic events.…”

Section: Introductionmentioning

confidence: 99%

Cell type- and stage-specific expression of Otx2 is coordinated by a cohort of transcription factors and multiplecis-regulatory modules in the retina

Chan

Lonfat

Zhao

et al. 2019

Preprint

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Transcription factors (TFs) are often used repeatedly during development and homeostasis to control distinct processes in the same and/or different cellular contexts.Considering the limited number of TFs in the genome and the tremendous number of events that need to be regulated, re-use of TFs is an advantageous strategy. However, the mechanisms that control the activation of TFs in different cell types and at different stages of development remain unclear. The neural retina serves as a model of the development of a complex tissue. We used this system to analyze how expression of the homeobox TF, Orthodenticle homeobox 2 (Otx2), is regulated in a cell type-and stagespecific manner during retinogenesis. We identified seven Otx2 cis-regulatory modules (CRMs), among which the O5, O7 and O9 CRMs mark three distinct cellular contexts of Otx2 expression. These include mature bipolar interneurons, photoreceptors, and retinal progenitor/precursor cells. We discovered that Otx2, Crx and Sox2, which are well-known TFs regulating retinal development, bind to and activate the O5, O7 or O9 CRMs respectively. The chromatin status of these three CRMs was found to be distinct in vivo in different retinal cell types and at different stages, as revealed by ATAC-seq and DNaseseq analyses. We conclude that retinal cells utilize a cohort of TFs with different expression patterns, and multiple CRMs with different chromatin configurations, to precisely regulate the expression of Otx2 in a cell type-and stage-specific manner in the retina.

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A mouse tissue transcription factor atlas

Cited by 98 publications

References 64 publications

A Compact Quadrupole-Orbitrap Mass Spectrometer with FAIMS Interface Improves Proteome Coverage in Short LC Gradients

A Compact Quadrupole-Orbitrap Mass Spectrometer with FAIMS Interface Improves Proteome Coverage in Short LC Gradients

Augmenter of liver regeneration protein deficiency promotes hepatic steatosis by inducing oxidative stress and microRNA‐540 expression

Cell type- and stage-specific expression of Otx2 is coordinated by a cohort of transcription factors and multiplecis-regulatory modules in the retina

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