scholarly journals The CrebA/Creb3-like transcription factors are major and direct regulators of secretory capacity

2010 ◽  
Vol 191 (3) ◽  
pp. 479-492 ◽  
Author(s):  
Rebecca M. Fox ◽  
Caitlin D. Hanlon ◽  
Deborah J. Andrew
Keyword(s):  
Transcription Factors ◽  
Secretory Pathway ◽  
Cell Types ◽  
Secretory Cells ◽  
Cell Type ◽  
Expression Of Genes ◽  
Genes Encoding ◽  
Cell Type Specific ◽  
General Protein ◽  
Secretory Capacity

Secretion occurs in all cells, with relatively low levels in most cells and extremely high levels in specialized secretory cells, such as those of the pancreas, salivary, and mammary glands. How secretory capacity is selectively up-regulated in specialized secretory cells is unknown. Here, we find that the CrebA/Creb3-like family of bZip transcription factors functions to up-regulate expression of both the general protein machinery required in all cells for secretion and of cell type–specific secreted proteins. Drosophila CrebA directly binds the enhancers of secretory pathway genes and is both necessary and sufficient to activate expression of every secretory pathway component gene examined thus far. Microarray profiling reveals that CrebA also up-regulates expression of genes encoding cell type–specific secreted components. Finally, we found that the human CrebA orthologues, Creb3L1 and Creb3L2, have the ability to up-regulate the secretory pathway in nonsecretory cell types.

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

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.

scholarly journals Single-nuclei chromatin profiling of ventral midbrain reveals cell identity transcription factors and cell-type-specific gene regulatory variation

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Yujuan Gui ◽  
Kamil Grzyb ◽  
Mélanie H. Thomas ◽  
Jochen Ohnmacht ◽  
Pierre Garcia ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Cell Types ◽  
Mouse Strains ◽  
Cell Type ◽  
Data Set ◽  
Cell Identity ◽  
Regulatory Variation ◽  
Ventral Midbrain ◽  
Cell Type Specific

Abstract Background Cell types in ventral midbrain are involved in diseases with variable genetic susceptibility, such as Parkinson’s disease and schizophrenia. Many genetic variants affect regulatory regions and alter gene expression in a cell-type-specific manner depending on the chromatin structure and accessibility. Results We report 20,658 single-nuclei chromatin accessibility profiles of ventral midbrain from two genetically and phenotypically distinct mouse strains. We distinguish ten cell types based on chromatin profiles and analysis of accessible regions controlling cell identity genes highlights cell-type-specific key transcription factors. Regulatory variation segregating the mouse strains manifests more on transcriptome than chromatin level. However, cell-type-level data reveals changes not captured at tissue level. To discover the scope and cell-type specificity of cis-acting variation in midbrain gene expression, we identify putative regulatory variants and show them to be enriched at differentially expressed loci. Finally, we find TCF7L2 to mediate trans-acting variation selectively in midbrain neurons. Conclusions Our data set provides an extensive resource to study gene regulation in mesencephalon and provides insights into control of cell identity in the midbrain and identifies cell-type-specific regulatory variation possibly underlying phenotypic and behavioural differences between mouse strains.

scholarly journals Histone modifications form a cell-type-specific chromosomal bar code that modulates and maintains patterns of gene expression through the cell cycle

2020 ◽  
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

ABSTRACTBackgroundChromatin 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.ResultsChromosome regions (bands) of 10-50Mb, detectable by immunofluorescence microscopy of metaphase (M) chromosomes, are also present in G1 and G2. We show that they comprise 1-5Mb 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 5Kb 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.ConclusionsModified histone isoforms H3K9ac, H3K4me3 and H3K27me3 exhibit a characteristic genomic distribution at resolutions of 1Mb 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.

Cell type-specific endometrial transcriptome changes during initial recognition of pregnancy in the mare

2019 ◽  
Vol 31 (3) ◽  
pp. 496 ◽  
Author(s):  
Iside Scaravaggi ◽  
Nicole Borel ◽  
Rebekka Romer ◽  
Isabel Imboden ◽  
Susanne E. Ulbrich ◽  
...  
Keyword(s):  
Gene Expression ◽  
Spatial Information ◽  
Gene Expression Regulation ◽  
Cell Types ◽  
Rna Seq ◽  
Cell Type ◽  
Expression Of Genes ◽  
Prostaglandin F ◽  
Cell Type Specific ◽  
Gene Expression Studies

Previous endometrial gene expression studies during the time of conceptus migration did not provide final conclusions on the mechanisms of maternal recognition of pregnancy (MRP) in the mare. This called for a cell type-specific endometrial gene expression analysis in response to embryo signals to improve the understanding of gene expression regulation in the context of MRP. Laser capture microdissection was used to collect luminal epithelium (LE), glandular epithelium and stroma from endometrial biopsies from Day 12 of pregnancy and Day 12 of the oestrous cycle. RNA sequencing (RNA-Seq) showed greater expression differences between cell types than between pregnant and cyclic states; differences between the pregnant and cyclic states were mainly found in LE. Comparison with a previous RNA-Seq dataset for whole biopsy samples revealed the specific origin of gene expression differences. Furthermore, genes specifically differentially expressed (DE) in one cell type were found that were not detectable as DE in biopsies. Overall, this study revealed spatial information about endometrial gene expression during the phase of initial MRP. The conceptus induced changes in the expression of genes involved in blood vessel development, specific spatial regulation of the immune system, growth factors, regulation of prostaglandin synthesis, transport prostaglandin receptors, specifically prostaglandin F receptor (PTGFR) in the context of prevention of luteolysis.

scholarly journals Single-Cell Regulatory Network Inference and Clustering Identifies Cell-Type Specific Expression Pattern of Transcription Factors in Mouse Sciatic Nerve

2021 ◽  
Vol 15 ◽  
Author(s):  
Mingchao Li ◽  
Qing Min ◽  
Matthew C. Banton ◽  
Xinpeng Dun
Keyword(s):  
Transcription Factors ◽  
Sciatic Nerve ◽  
Single Cell ◽  
Cell Types ◽  
Cell Type ◽  
Specific Expression ◽  
Single Cell Rna Sequencing ◽  
Cell Type Specific Expression ◽  
Cell Type Specific ◽  
Different Cell Types

Advances in single-cell RNA sequencing technologies and bioinformatics methods allow for both the identification of cell types in a complex tissue and the large-scale gene expression profiling of various cell types in a mixture. In this report, we analyzed a single-cell RNA sequencing (scRNA-seq) dataset for the intact adult mouse sciatic nerve and examined cell-type specific transcription factor expression and activity during peripheral nerve homeostasis. In total, we identified 238 transcription factors expressed in nine different cell types of intact mouse sciatic nerve. Vascular smooth muscle cells have the lowest number of transcription factors expressed with 17 transcription factors identified. Myelinating Schwann cells (mSCs) have the highest number of transcription factors expressed, with 61 transcription factors identified. We created a cell-type specific expression map for the identified 238 transcription factors. Our results not only provide valuable information about the expression pattern of transcription factors in different cell types of adult peripheral nerves but also facilitate future studies to understand the function of key transcription factors in the peripheral nerve homeostasis and disease.

scholarly journals Cell type-specific modulation of healthspan by Forkhead family transcription factors in the nervous system

2021 ◽  
Vol 118 (8) ◽  
pp. e2011491118 ◽  
Author(s):  
Ekin Bolukbasi ◽  
Nathaniel S. Woodling ◽  
Dobril K. Ivanov ◽  
Jennifer Adcott ◽  
Andrea Foley ◽  
...  
Keyword(s):  
Nervous System ◽  
Transcription Factors ◽  
Cell Types ◽  
Growth Factor Signaling ◽  
Cell Type ◽  
Model Of Alzheimer’S Disease ◽  
Distinct Cell ◽  
Evolutionarily Conserved ◽  
Cell Type Specific ◽  
Specific Mapping

Reduced activity of insulin/insulin-like growth factor signaling (IIS) increases healthy lifespan among diverse animal species. Downstream of IIS, multiple evolutionarily conserved transcription factors (TFs) are required; however, distinct TFs are likely responsible for these effects in different tissues. Here we have asked which TFs can extend healthy lifespan within distinct cell types of the adult nervous system in Drosophila. Starting from published single-cell transcriptomic data, we report that forkhead (FKH) is endogenously expressed in neurons, whereas forkhead-box-O (FOXO) is expressed in glial cells. Accordingly, we find that neuronal FKH and glial FOXO exert independent prolongevity effects. We have further explored the role of neuronal FKH in a model of Alzheimer’s disease-associated neuronal dysfunction, where we find that increased neuronal FKH preserves behavioral function and reduces ubiquitinated protein aggregation. Finally, using transcriptomic profiling, we identify Atg17, a member of the Atg1 autophagy initiation family, as one FKH-dependent target whose neuronal overexpression is sufficient to extend healthy lifespan. Taken together, our results underscore the importance of cell type-specific mapping of TF activity to preserve healthy function with age.

scholarly journals ANANSE: An enhancer network-based computational approach for predicting key transcription factors in cell fate determination

2020 ◽  
Author(s):  
Quan Xu ◽  
Georgios Georgiou ◽  
Gert Jan C. Veenstra ◽  
Huiqing Zhou ◽  
Simon J. van Heeringen
Keyword(s):  
Transcription Factors ◽  
Cell Fate ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Cell Types ◽  
Cell Fate Determination ◽  
Cell Type ◽  
Fate Determination ◽  
Cell Type Specific ◽  
Gene Regulatory

AbstractProper cell fate determination is largely orchestrated by complex gene regulatory networks centered around transcription factors. However, experimental elucidation of key transcription factors that drive cellular identity is currently often intractable. Here, we present ANANSE (ANalysis Algorithm for Networks Specified by Enhancers), a network-based method that exploits enhancer-encoded regulatory information to identify the key transcription factors in cell fate determination. As cell type-specific transcription factors predominantly bind to enhancers, we use regulatory networks based on enhancer properties to prioritize transcription factors. First, we predict genome-wide binding profiles of transcription factors in various cell types using enhancer activity and transcription factor binding motifs. Subsequently, applying these inferred binding profiles, we construct cell type-specific gene regulatory networks, and then predict key transcription factors controlling cell fate conversions using differential gene networks between cell types. This method outperforms existing approaches in correctly predicting major transcription factors previously identified to be sufficient for trans-differentiation. Finally, we apply ANANSE to define an atlas of key transcription factors in 18 normal human tissues. In conclusion, we present a ready-to-implement computational tool for efficient prediction of transcription factors in cell fate determination and to study transcription factor-mediated regulatory mechanisms. ANANSE is freely available at https://github.com/vanheeringen-lab/ANANSE.

scholarly journals Unique molecular features and cellular responses differentiate two populations of motor cortical layer 5b neurons in a preclinical model of ALS.

2021 ◽  
Author(s):  
Maria V Moya ◽  
Rachel D Kim ◽  
Meghana N Rao ◽  
Bianca A Cotto ◽  
Sarah B Pickett ◽  
...  
Keyword(s):  
Motor Neurons ◽  
Cell Types ◽  
Projection Neuron ◽  
Cortical Layer ◽  
Preclinical Model ◽  
Cell Type ◽  
Molecular Features ◽  
Expression Of Genes ◽  
Neuron Populations ◽  
Cell Type Specific

Many neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), lead to the selective degeneration of discrete cell types in the CNS despite the ubiquitous expression of many genes linked to disease. Therapeutic advancement depends on understanding unique cellular adaptations that underlie pathology of vulnerable cells in the context of disease-causing mutations. Here, we employ bacTRAP molecular profiling to elucidate cell type specific molecular responses of cortical upper motor neurons in a preclinical ALS model. Using two bacTRAP mouse lines that label distinct vulnerable or resilient projection neuron populations in motor cortex, we show that the regulation of oxidative phosphorylation (Oxphos) pathways is a common response in both cell types. However, differences in the baseline expression of genes involved in Oxphos and the handling of reactive oxygen species likely lead to the selective degeneration of the vulnerable cells. These results provide a framework to identify cell type-specific processes in neurodegenerative disease.

scholarly journals A Global Temporal Genetic Program for Neural Circuit Formation

2020 ◽  
Author(s):  
Saumya Jain ◽  
Ying Lin ◽  
Yerbol Kurmangaliyev ◽  
Parmis Mirshahidi ◽  
Brianna Parrington ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Visual System ◽  
Neural Circuit ◽  
Cell Types ◽  
Temporal Control ◽  
Cell Type ◽  
Cell Type Specificity ◽  
Specific Expression ◽  
Genes Encoding ◽  
Circuit Formation

Wiring a complex brain relies on cell-type and temporal-specific expression of genes encoding cell recognition molecules regulating circuit formation1–3. Though genetic programs driving cell-type specificity have been described4–6, how precise temporal control is achieved remains unknown. Here, we describe a global program for the temporal regulation of cell-type-specific wiring genes in the Drosophila visual system. We show that the Ecdysone Receptor induces a synchronous cascade of transcription factors in neurons throughout the visual system in a highly stereotyped fashion. Single-cell RNA-seq analysis of neurons lacking transcription factors in the cascade revealed that targets are cell-type dependent and these are enriched for wiring genes. Knock-down of different transcription factors in this cascade led to defects in sequential steps in wiring. Taken together, this work identifies a synchronous, global program for temporal control of different sets of wiring genes in different neurons. We speculate that this global program coordinates development across cell types to choreograph specific steps in circuit assembly.

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