A HOX complex, a repressor element and a 50 bp sequence confer regional specificity to a DPP-responsive enhancer

Development ◽  
2001 ◽  
Vol 128 (14) ◽  
pp. 2833-2845 ◽  
Author(s):  
Thomas Marty ◽  
M. Alessandra Vigano ◽  
Carlos Ribeiro ◽  
Ute Nussbaumer ◽  
Nicole C. Grieder ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Cultured Cells ◽  
Cell Type ◽  
Response Element ◽  
Regional Specificity ◽  
A Cell ◽  
Cell Type Specific ◽  
Hox Protein ◽  
Repressor Element

A central theme during development and homeostasis is the generation of cell type-specific responses to the action of a limited number of extant signaling cascades triggered by extracellular ligands. The molecular mechanisms by which information from such signals are integrated in responding cells in a cell-type specific manner remain poorly understood. We have undertaken a detailed characterization of an enhancer that is regulated by DPP signaling and by the homeotic protein Labial and its partners, Extradenticle and Homothorax. The expression driven by this enhancer (lab550) and numerous deletions and point mutants thereof was studied in wild-type and mutant Drosophila embryos as well as in cultured cells. We find that the lab550 enhancer is composed of two elements, a Homeotic Response Element (HOMRE) and a DPP Response Element (DPPRE) that synergize. None of these two elements can reproduce the expression of lab550, either with regard to expression level or with regard to spatial restriction. The isolated DPPRE of lab550 responds extremely weakly to DPP. Interestingly, we found that the inducibility of this DPPRE is weak because it is tuned down by the action of a repressor element. This repressor element and an additional 50 bp element appear to be crucial for the cooperation of the HOMRE and the DPPRE, and might tightly link the DPP response to the homeotic input. The cooperation between the different elements of the enhancer leads to the segmentally restricted activity of lab550 in the endoderm and provides a mechanism to create specific responses to DPP signaling with the help of a HOX protein complex.

scholarly journals Profiling of Primary and Mature miRNA Expression in Atherosclerosis Associated Cell Types

2021 ◽  
Author(s):  
Pierre R. Moreau ◽  
Vanesa Tomas Bosch ◽  
Maria Bouvy-Liivrand ◽  
Kadri Õunap ◽  
Tiit Örd ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Molecular Mechanisms ◽  
Umbilical Vein ◽  
Cell Types ◽  
Integrative Approach ◽  
Dependent Manner ◽  
Cell Type ◽  
A Cell ◽  
Cell Type Specific

Objective: Atherosclerosis is the underlying cause of most cardiovascular diseases. The main cell types associated with disease progression in the vascular wall are endothelial cells, smooth muscle cells, and macrophages. Although their role in atherogenesis has been extensively described, molecular mechanisms underlying gene expression changes remain unknown. The objective of this study was to characterize microRNA (miRNA)-related regulatory mechanisms taking place in the aorta during atherosclerosis: Approach and Results: We analyzed the changes in primary human aortic endothelial cells and human umbilical vein endothelial cell, human aortic smooth muscle cell, and macrophages (CD14+) under various proatherogenic stimuli by integrating GRO-seq, miRNA-seq, and RNA-seq data. Despite the highly cell-type-specific expression of multi-variant pri-miRNAs, the majority of mature miRNAs were found to be common to all cell types and dominated by 2 to 5 abundant miRNA species. We demonstrate that transcription contributes significantly to the mature miRNA levels although this is dependent on miRNA stability. An analysis of miRNA effects in relation to target mRNA pools highlighted pathways and targets through which miRNAs could affect atherogenesis in a cell-type-dependent manner. Finally, we validate miR-100-5p as a cell-type specific regulator of inflammatory and HIPPO-YAP/TAZ-pathways. Conclusions: This integrative approach allowed us to characterize miRNA dynamics in response to a proatherogenic stimulus and identify potential mechanisms by which miRNAs affect atherogenesis in a cell-type-specific manner.

Phosphatase Wip1 negatively regulates neutrophil development through p38 MAPK-STAT1

Blood ◽  
2013 ◽  
Vol 121 (3) ◽  
pp. 519-529 ◽  
Author(s):  
Guangwei Liu ◽  
Xuelian Hu ◽  
Bo Sun ◽  
Tao Yang ◽  
Jianfeng Shi ◽  
...  
Keyword(s):  
P38 Mapk ◽  
Molecular Mechanisms ◽  
Negative Regulator ◽  
Cell Type ◽  
A Cell ◽  
Cell Type Specific ◽  
Neutrophil Differentiation ◽  
Deficient Mice

Abstract Neutrophils are critically involved in host defense and tissue damage. Intrinsic molecular mechanisms controlling neutrophil differentiation and activities are poorly defined. Herein we found that p53-induced phosphatase 1(Wip1) is preferentially expressed in neutrophils among immune cells. The Wip1 expression is gradually up-regulated during the differentiation of myeloid precursors into mature neutrophils. Wip1-deficient mice and chimera mice with Wip1−/− hematopoietic cells had an expanded pool of neutrophils with hypermature phenotypes in the periphery. The in vivo and in vitro studies showed that Wip1 deficiency mainly impaired the developing process of myeloid progenitors to neutrophils in an intrinsic manner. Mechanism studies showed that the enhanced development and maturation of neutrophils caused by Wip1 deficiency were mediated by p38 MAPK-STAT1 but not p53-dependent pathways. Thus, our findings identify a previously unrecognized p53-independent function of Wip1 as a cell type-specific negative regulator of neutrophil generation and homeostasis through limiting the p38 MAPK-STAT1 pathway.

scholarly journals Genistein Enhances or Reduces Glycosaminoglycan Quantity in a Cell Type-Specific Manner

2018 ◽  
Vol 47 (4) ◽  
pp. 1667-1681
Author(s):  
Ying Lan ◽  
Xiulian Li ◽  
Xuebo Liu ◽  
Cui Hao ◽  
Ni Song ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Isotope Labeling ◽  
Dependent Manner ◽  
Cell Type ◽  
Beneficial Effects ◽  
Genistein Treatment ◽  
Specific Manner ◽  
A Cell ◽  
Cell Type Specific ◽  
Hct116 Cells

Background/Aims: Genistein is a natural isoflavone enriched in soybeans. It has beneficial effects for patients with mucopolysaccharidose type III through inhibiting glycosaminoglycan biosynthesis. However, other studies indicate that genistein does not always inhibit glycosaminoglycan biosynthesis. Methods: To understand the underlying molecular mechanisms, CHOK1, CHO3.1, CHO3.3, and HCT116 cells were treated with genistein and the monosaccharide compositions and quantity of all glycans from the cell lysate were measured after thorough acid hydrolysis followed by HPLC analysis. In addition, the glycosaminoglycan disaccharide compositions were obtained by stable isotope labeling coupled with LC/MS analysis. Results: Genistein treatment reduced the amount of glycans but increased the amount of glycosaminoglycans in HCT116 cells. In contrast, genistein treatment reduced both glycan and glycosaminoglycan quantities in CHOK1, CHO3.1, and CHO3.3 cells in addition to differential changes in glycosaminoglycan disaccharide compositions. Conclusion: Genistein treatment reduced overall glycan quantity but glycosaminoglycan quantities were either increased or decreased in a cell type-dependent manner.

scholarly journals Single-cell transcriptomics and cell-specific proteomics reveals molecular signatures of sleep

2020 ◽  
Author(s):  
Pawan K. Jha ◽  
Utham K. Valekunja ◽  
Sandipan Ray ◽  
Mathieu Nollet ◽  
Akhilesh B. Reddy
Keyword(s):  
Single Cell ◽  
Molecular Mechanisms ◽  
Cell Types ◽  
Brain Regions ◽  
Specific Protein ◽  
Cell Type ◽  
Transcriptional Responses ◽  
A Cell ◽  
Cell Type Specific ◽  
Different Cell Types

Every day, we sleep for a third of the day. Sleep is important for cognition, brain waste clearance, metabolism, and immune responses. The molecular mechanisms governing sleep are largely unknown. Here, we used a combination of single cell RNA sequencing and cell-type specific proteomics to interrogate the molecular underpinnings of sleep. Different cell types in three important brain regions for sleep (brainstem, cortex, and hypothalamus) exhibited diverse transcriptional responses to sleep need. Sleep restriction modulates astrocyte-neuron crosstalk and sleep need enhances expression of specific sets of transcription factors in different brain regions. In cortex, we also interrogated the proteome of two major cell types: astrocytes and neurons. Sleep deprivation differentially alters the expression of proteins in astrocytes and neurons. Similarly, phosphoproteomics revealed large shifts in cell-type specific protein phosphorylation. Our results indicate that sleep need regulates transcriptional, translational, and post-translational responses in a cell-specific manner.

IFIH1-deficiency results in a cell-type specific alteration of autophagic activity in response to S. typhimurium

2017 ◽  
Vol 55 (05) ◽  
pp. e28-e56
Author(s):  
S Macheiner ◽  
R Gerner ◽  
A Pfister ◽  
A Moschen ◽  
H Tilg
Keyword(s):  
Cell Type ◽  
A Cell ◽  
Cell Type Specific ◽  
Autophagic Activity ◽  
Specific Alteration

scholarly journals A cell type‐specific expression map of NCoR1 and SMRT transcriptional co‐repressors in the mouse brain

2020 ◽  
Vol 528 (13) ◽  
pp. 2218-2238 ◽  
Author(s):  
Attilio Iemolo ◽  
Patricia Montilla‐Perez ◽  
I‐Chi Lai ◽  
Yinuo Meng ◽  
Syreeta Nolan ◽  
...  
Keyword(s):  
Mouse Brain ◽  
Cell Type ◽  
Specific Expression ◽  
Cell Type Specific Expression ◽  
A Cell ◽  
Cell Type Specific
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