scholarly journals Developmentally Programmed 3′ CpG Island Methylation Confers Tissue- and Cell-Type-Specific Transcriptional Activation

2013 ◽  
Vol 33 (9) ◽  
pp. 1845-1858 ◽  
Author(s):  
Da-Hai Yu ◽  
Carol Ware ◽  
Robert A. Waterland ◽  
Jiexin Zhang ◽  
Miao-Hsueh Chen ◽  
...  
Keyword(s):  
Transcriptional Regulation ◽  
Transcriptional Activation ◽  
Functional Role ◽  
Cpg Island ◽  
Embryonic Stem ◽  
Luciferase Reporter ◽  
Specific Gene ◽  
Cell Type ◽  
Cell Type Specific

During development, a small but significant number of CpG islands (CGIs) become methylated. The timing of developmentally programmed CGI methylation and associated mechanisms of transcriptional regulation during cellular differentiation, however, remain poorly characterized. Here, we used genome-wide DNA methylation microarrays to identify epigenetic changes during human embryonic stem cell (hESC) differentiation. We discovered a group of CGIs associated with developmental genes that gain methylation after hESCs differentiate. Conversely, erasure of methylation was observed at the identified CGIs during subsequent reprogramming to induced pluripotent stem cells (iPSCs), further supporting a functional role for the CGI methylation. Both global gene expression profiling and quantitative reverse transcription-PCR (RT-PCR) validation indicated opposing effects of CGI methylation in transcriptional regulation during differentiation, with promoter CGI methylation repressing and 3′ CGI methylation activating transcription. By studying diverse human tissues and mouse models, we further confirmed that developmentally programmed 3′ CGI methylation confers tissue- and cell-type-specific gene activationin vivo. Importantly, luciferase reporter assays provided evidence that 3′ CGI methylation regulates transcriptional activation via a CTCF-dependent enhancer-blocking mechanism. These findings expand the classic view of mammalian CGI methylation as a mechanism for transcriptional silencing and indicate a functional role for 3′ CGI methylation in developmental gene regulation.

scholarly journals Differential Transcriptional Regulation of the NANOG Gene in Chicken Primordial Germ Cells and Embryonic Stem Cells

2020 ◽  
Author(s):  
Hee Jung Choi ◽  
So Dam Jin ◽  
Deivendran Rengaraj ◽  
Jin Hwa Kim ◽  
Bertrand Pain ◽  
...  
Keyword(s):  
Stem Cells ◽  
Transcriptional Regulation ◽  
Embryonic Stem Cells ◽  
Germ Cells ◽  
Primordial Germ Cells ◽  
Embryonic Stem ◽  
Regulatory Elements ◽  
Luciferase Reporter ◽  
Cell Type ◽  
Cell Type Specific

Abstract BackgroundNANOG is a core transcription factor (TF) in embryonic stem cells (ESCs) and primordial germ cells (PGCs). Regulation of the NANOG gene by TFs, epigenetic factors, and autoregulatory factors is well characterized in ESCs, and transcriptional regulation of NANOG is well established in these cells. Although NANOG plays a key role in germ cells, the molecular mechanism underlying its transcriptional regulation in PGCs has not been studied. Therefore, we investigated the mechanism that regulates transcription of the chicken NANOG (cNANOG) gene in PGCs and ESCs. ResultsWe first identified the transcription start site of cNANOG by 5’-rapid amplification of cDNA ends PCR analysis. Then, we measured the promoter activity of various 5’ flanking regions of cNANOG in chicken PGCs and ESCs using the luciferase reporter assay. cNANOG expression required transcriptional cis-regulatory elements, which were positively regulated by POU5F3 (OCT4) and SOX2 and negatively regulated by TP53 in PGCs. The proximal region of the cNANOG promoter contains a positive cis-regulatory element (CCAAT/enhancer-binding protein (CEBP)-binding site) in ESCs. Furthermore, small interfering RNA-mediated knockdown demonstrated that POU5F3, SOX2, and CEBP played a role in cell type-specific transcription of cNANOG.ConclusionsWe show for the first time that different cis-regulatory elements control transcription of cNANOG in a cell type-specific manner. This finding might help to elucidate the mechanism that regulates cNANOG expression in PGCs and ESCs.

scholarly journals Monitoring Cell-Type–Specific Gene Expression Using Ribosome Profiling In Vivo During Cardiac Hemodynamic Stress

2019 ◽  
Vol 125 (4) ◽  
pp. 431-448 ◽  
Author(s):  
Shirin Doroudgar ◽  
Christoph Hofmann ◽  
Etienne Boileau ◽  
Brandon Malone ◽  
Eva Riechert ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ribosome Profiling ◽  
Specific Gene ◽  
Cell Type ◽  
Specific Gene Expression ◽  
Hemodynamic Stress ◽  
Cell Type Specific

scholarly journals Cell type specific gene expression profiling reveals a role for the complement component C3A in neutrophil migration to tissue damage

2019 ◽  
Author(s):  
Ruth A. Houseright ◽  
Emily E. Rosowski ◽  
Pui Ying Lam ◽  
Sebastien JM Tauzin ◽  
Oscar Mulvaney ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bacterial Infections ◽  
Large Scale ◽  
Affinity Purification ◽  
Neutrophil Migration ◽  
Acute Injury ◽  
Specific Gene ◽  
Cell Type ◽  
Cell Type Specific

AbstractFollowing acute injury, leukocytes rapidly infiltrate into tissues. For efficient recruitment, leukocytes must sense and respond to signals from both from the damaged tissue and from one another. However, the cell type specific transcriptional changes that influence leukocyte recruitment and wound healing have not been well characterized. In this study, we performed a large-scale translating ribosome affinity purification (TRAP) and RNA sequencing screen in larval zebrafish to identify genes differentially expressed by neutrophils, macrophages, and epithelial cells in the context of wounding. We identified the complement pathway and c3a.1, homologous to the C3A component of human complement, as significantly increased in neutrophils in response to a wound. We report that c3a.1−/− zebrafish larvae have impaired neutrophil responses to both tail wounds and localized bacterial infections, as well as increased susceptibility to infection due to a neutrophil-intrinsic function of C3A. We further show that C3A enhances migration of human primary neutrophils to IL-8 and that c3a.1−/− larvae have impaired neutrophil migration in vivo, and a decrease in neutrophil directed migration speed early after wounding. Together, our findings suggest a role for C3A in mediating efficient neutrophil migration to damaged tissues and support the power of TRAP to identify cell-specific changes in gene expression associated with wound-associated inflammation.

scholarly journals MLL3/MLL4 methyltransferase activities regulate embryonic stem cell differentiation independent of enhancer H3K4me1

2020 ◽  
Author(s):  
Guojia Xie ◽  
Ji-Eun Lee ◽  
Kaitlin McKernan ◽  
Young-Kwon Park ◽  
Younghoon Jang ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Embryonic Development ◽  
Embryonic Stem ◽  
Stem Cell Differentiation ◽  
Enzymatic Activities ◽  
Early Embryonic Development ◽  
Specific Gene ◽  
Cell Type ◽  
Mouse Development ◽  
Cell Type Specific

Enhancers drive cell-type-specific gene transcription and are marked by H3K4me1. MLL4 (KMT2D), a major H3K4me1 methyltransferase with partial functional redundancy with MLL3 (KMT2C), is critical for enhancer activation and cell-type-specific gene induction during cell differentiation and development. However, the roles of MLL3/4-mediated enhancer H3K4me1 and MLL3/4 enzymatic activities in general in these processes remain unclear. Here, we report that MLL3/4 enzymatic activities are partially redundant during mouse development. Simultaneous elimination of both leads to embryonic lethality around E8.5. Using embryoid body (EB) differentiation as an in vitro model for early embryonic development, we show that Mll3 knockout MLL4 enzyme-dead embryonic stem cells (ESCs) are capable of differentiating towards the three germ layers but display severe cavitation defects, likely due to impaired induction of visceral endoderm. Importantly, MLL3/4-catalyzed H3K4me1 is dispensable for enhancer activation during early EB differentiation and lineage-specific neural differentiation. Together, these results suggest a critical, but enhancer H3K4me1-independent, role of MLL3/4 enzymatic activities in early embryonic development and ESC differentiation.

scholarly journals Neuronal cell type–specific alternative splicing is regulated by the KH domain protein SLM1

2014 ◽  
Vol 204 (3) ◽  
pp. 331-342 ◽  
Author(s):  
Takatoshi Iijima ◽  
Yoko Iijima ◽  
Harald Witte ◽  
Peter Scheiffele
Keyword(s):  
Alternative Splicing ◽  
Neuronal Cell ◽  
Specific Gene ◽  
Cell Type ◽  
Specific Expression ◽  
Splicing Regulators ◽  
Cell Type Specific Expression ◽  
Kh Domain ◽  
Cell Type Specific

The unique functional properties and molecular identity of neuronal cell populations rely on cell type–specific gene expression programs. Alternative splicing represents a powerful mechanism for expanding the capacity of genomes to generate molecular diversity. Neuronal cells exhibit particularly extensive alternative splicing regulation. We report a highly selective expression of the KH domain–containing splicing regulators SLM1 and SLM2 in the mouse brain. Conditional ablation of SLM1 resulted in a severe defect in the neuronal isoform content of the polymorphic synaptic receptors neurexin-1, -2, and -3. Thus, cell type–specific expression of SLM1 provides a mechanism for shaping the molecular repertoires of synaptic adhesion molecules in neuronal populations in vivo.

Characterization and subcellular localization of a bacterial flotillin homologue

Microbiology ◽  
2009 ◽  
Vol 155 (6) ◽  
pp. 1786-1799 ◽  
Author(s):  
Catriona Donovan ◽  
Marc Bramkamp
Keyword(s):  
Early Stage ◽  
Model Organism ◽  
Cell Types ◽  
Specific Gene ◽  
Cell Type ◽  
Distinct Cell ◽  
Sporulation Efficiency ◽  
Cell Type Specific ◽  
Detergent Resistant Membranes

The process of endospore formation in Bacillus subtilis is complex, requiring the generation of two distinct cell types, a forespore and larger mother cell. The development of these cell types is controlled and regulated by cell type-specific gene expression, activated by a σ-factor cascade. Activation of these cell type-specific sigma factors is coupled with the completion of polar septation. Here, we describe a novel protein, YuaG, a eukaryotic reggie/flotillin homologue that is involved in the early stages of sporulation of the Gram-positive model organism B. subtilis. YuaG localizes in discrete foci in the membrane and is highly dynamic. Purification of detergent-resistant membranes revealed that YuaG is associated with negatively charged phospholipids, e.g. phosphatidylglycerol (PG) or cardiolipin (CL). However, localization of YuaG is not always dependent on PG/CL in vivo. A yuaG disruption strain shows a delay in the onset of sporulation along with reduced sporulation efficiency, where the spores develop to a certain stage and then appear to be trapped at this stage. Our results indicate that YuaG is involved in the early stage of spore development, probably playing a role in the signalling cascade at the onset of sporulation.

scholarly journals Intragenic CpG islands play important roles in bivalent chromatin assembly of developmental genes

2017 ◽  
Vol 114 (10) ◽  
pp. E1885-E1894 ◽  
Author(s):  
Sun-Min Lee ◽  
Jungwoo Lee ◽  
Kyung-Min Noh ◽  
Won-Young Choi ◽  
Sejin Jeon ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Transcriptional Activation ◽  
Epigenetic Modification ◽  
Embryonic Stem ◽  
Housekeeping Genes ◽  
Regulation Of Transcription ◽  
Physical Interaction ◽  
Cell Type ◽  
Cell Type Specific ◽  
Specific Regulation

CpG, 5′-C-phosphate-G-3′, islands (CGIs) have long been known for their association with enhancers, silencers, and promoters, and for their epigenetic signatures. They are maintained in embryonic stem cells (ESCs) in a poised but inactive state via the formation of bivalent chromatin containing both active and repressive marks. CGIs also occur within coding sequences, where their functional role has remained obscure. Intragenic CGIs (iCGIs) are largely absent from housekeeping genes, but they are found in all genes associated with organ development and cell lineage control. In this paper, we investigated the epigenetic status of iCGIs and found that they too reside in bivalent chromatin in ESCs. Cell type-specific DNA methylation of iCGIs in differentiated cells was linked to the loss of both the H3K4me3 and H3K27me3 marks, and disruption of physical interaction with promoter regions, resulting in transcriptional activation of key regulators of differentiation such as PAXs, HOXs, and WNTs. The differential epigenetic modification of iCGIs appears to be mediated by cell type-specific transcription factors distinct from those bound by promoter, and these transcription factors may be involved in the hypermethylation of iCGIs upon cell differentiation. iCGIs thus play a key role in the cell type-specific regulation of transcription.

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