scholarly journals Steroid-like signalling by interferons: making sense of specific gene activation by cytokines

2012 ◽  
Vol 445 (2) ◽  
pp. 295-295 ◽  
Author(s):  
H. M. Johnson ◽  
E. N. Noon-Song ◽  
K. Kemppainen ◽  
C. M. Ahmed
Keyword(s):  
Gene Activation ◽  
Specific Gene ◽  
Making Sense

scholarly journals Noncanonical IFN Signaling, Steroids, and STATs: A Probable Role of V-ATPase

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Howard M. Johnson ◽  
Ezra Noon-Song ◽  
Chulbul M. Ahmed
Keyword(s):  
Tyrosine Kinases ◽  
Nuclear Translocation ◽  
Gene Activation ◽  
Membrane Receptors ◽  
Specific Gene ◽  
Type I ◽  
Endosomal Membrane ◽  
Making Sense ◽  
Stat Signaling ◽  
Probable Role

A small group of only seven transcription factors known as STATs (signal transducer and activator of transcription) are considered to be canonical determinants of specific gene activation for a plethora of ligand/receptor systems. The activation of STATs involves a family of four tyrosine kinases called JAK kinases. JAK1 and JAK2 activate STAT1 in the cytoplasm at the heterodimeric gamma interferon (IFNγ) receptor, while JAK1 and TYK2 activate STAT1 and STAT2 at the type I IFN heterodimeric receptor. The same STATs and JAKs are also involved in signaling by functionally different cytokines, growth factors, and hormones. Related to this, IFNγ-activated STAT1 binds to the IFNγ-activated sequence (GAS) element, but so do other STATs that are not involved in IFNγ signaling. Activated JAKs such as JAK2 and TYK2 are also involved in the epigenetics of nucleosome unwrapping for exposure of DNA to transcription. Furthermore, activated JAKs and STATs appear to function coordinately for specific gene activation. These complex events have not been addressed in canonical STAT signaling. Additionally, the function of noncoding enhancer RNAs, including their role in enhancer/promoter interaction is not addressed in the canonical STAT signaling model. In this perspective, we show that JAK/STAT signaling, involving membrane receptors, is essentially a variation of cytoplasmic nuclear receptor signaling. Focusing on IFN signaling, we showed that ligand, IFN receptor, the JAKs, and the STATs all undergo endocytosis and ATP-dependent nuclear translocation to promoters of genes specifically activated by IFNs. We argue here that the vacuolar ATPase (V-ATPase) proton pump probably plays a key role in endosomal membrane crossing by IFNs for receptor cytoplasmic binding. Signaling of nuclear receptors such as those of estrogen and dihydrotestosterone provides templates for making sense of the specificity of gene activation by closely related cytokines, which has implications for lymphocyte phenotypes.

scholarly journals Aspergillus nidulans wetA activates spore-specific gene expression.

1991 ◽  
Vol 11 (1) ◽  
pp. 55-62 ◽  
Author(s):  
M A Marshall ◽  
W E Timberlake
Keyword(s):  
Gene Expression ◽  
Cell Wall ◽  
Aspergillus Nidulans ◽  
Gene Activation ◽  
Regulatory Function ◽  
Specific Gene ◽  
Coding Region ◽  
Vegetative Cells ◽  
Mutant Strains ◽  
Late Stages

The Aspergillus nidulans wetA gene is required for synthesis of cell wall layers that make asexual spores (conidia) impermeable. In wetA mutant strains, conidia take up water and autolyze rather than undergoing the final stages of maturation. wetA is activated during conidiogenesis by sequential expression of the brlA and abaA regulatory genes. To determine whether wetA regulates expression of other sporulation-specific genes, its coding region was fused to a nutritionally regulated promoter that permits gene activation in vegetative cells (hyphae) under conditions that suppress conidiation. Expression of wetA in hyphae inhibited growth and caused excessive branching. It did not lead to activation of brlA or abaA but did cause accumulation of transcripts from genes that are normally expressed specifically during the late stages of conidiation and whose mRNAs are stored in mature spores. Thus, wetA directly or indirectly regulates expression of some spore-specific genes. At least one gene (wA), whose mRNA does not occur in spores but rather accumulates in the sporogenous phialide cells, was activated by wetA, suggesting that wetA may have a regulatory function in these cells as well as in spores. We propose that wetA is responsible for activating a set of genes whose products make up the final two conidial wall layers or direct their assembly and through this activity is responsible for acquisition of spore dormancy.

The Florey Lecture, 1988 - From egg to embryo: the initiation of cell differentiation in Amphibia

1989 ◽  
Vol 237 (1286) ◽  
pp. 11-25 ◽  
Keyword(s):  
Muscle Cell ◽  
Gene Activation ◽  
Cell Formation ◽  
Gene Promoter ◽  
Cell Types ◽  
Specific Gene ◽  
Embryonic Induction ◽  
Differentiated Cells ◽  
Wide Range ◽  
Muscle Genes

Some of the principles by which different cell types first arise at the beginning of animal development are illustrated by muscle cell formation in Amphibia. If the nucleus of a differentiated muscle cell is transplanted to an enucleated egg, some of the resulting embryos develop into tadpoles with a wide range of normally differentiated cells. These experiments show that genes undergo major changes in activity as a response to components of egg cytoplasm. Two fundamental mechanisms account for the regional activation of genes in early embryos. One involves the effect of localized ‘determinants’ in egg cytoplasm, and the other concerns cell interactions or embryonic induction. Both these mechanisms seem to be responsible for muscle cell formation in amphibian development. The old problem of embryonic induction has recently become accessible to analysis at the molecular level, especially in the case of the mesoderm or muscle-forming induction. This has been greatly facilitated by using a sensitive and quantitative assay to detect the first transcripts of muscle genes a few hours after the start of induction. The role of early events and of interactions among like cells during response to induction is discussed. In analysing specific gene activation following induction, DNA injection into fertilized eggs has shown that a very small part of the cardiac actin gene promoter is sufficient to enable it to respond to induction. Although the experimental work summarized here has been done on amphibian embryos, which are more suitable than other embryos for embryological manipulation, the conclusions reached are believed to be generally applicable to the development of other organisms.

scholarly journals Mediator subunit MED1 is required for E2A-PBX1–mediated oncogenic transcription and leukemic cell growth

2021 ◽  
Vol 118 (6) ◽  
pp. e1922864118 ◽  
Author(s):  
Yu-Ling Lee ◽  
Keiichi Ito ◽  
Wen-Chieh Pi ◽  
I-Hsuan Lin ◽  
Chi-Shuen Chu ◽  
...  
Keyword(s):  
Cell Growth ◽  
Rna Polymerase Ii ◽  
Transcriptional Activation ◽  
Critical Role ◽  
Gene Activation ◽  
Leukemic Cell ◽  
Leukemic Cells ◽  
Specific Gene ◽  
Aberrant Expression ◽  
Transcriptional Machinery

The chimeric transcription factor E2A-PBX1, containing the N-terminal activation domains of E2A fused to the C-terminal DNA-binding domain of PBX1, results in 5% of pediatric acute lymphoblastic leukemias (ALL). We recently have reported a mechanism for RUNX1-dependent recruitment of E2A-PBX1 to chromatin in pre-B leukemic cells; but the subsequent E2A-PBX1 functions through various coactivators and the general transcriptional machinery remain unclear. The Mediator complex plays a critical role in cell-specific gene activation by serving as a key coactivator for gene-specific transcription factors that facilitates their function through the RNA polymerase II transcriptional machinery, but whether Mediator contributes to aberrant expression of E2A-PBX1 target genes remains largely unexplored. Here we show that Mediator interacts directly with E2A-PBX1 through an interaction of the MED1 subunit with an E2A activation domain. Results of MED1 depletion by CRISPR/Cas9 further indicate that MED1 is specifically required for E2A-PBX1–dependent gene activation and leukemic cell growth. Integrated transcriptome and cistrome analyses identify pre-B cell receptor and cell cycle regulatory genes as direct cotargets of MED1 and E2A-PBX1. Notably, complementary biochemical analyses also demonstrate that recruitment of E2A-PBX1 to a target DNA template involves a direct interaction with DNA-bound RUNX1 that can be further stabilized by EBF1. These findings suggest that E2A-PBX1 interactions with RUNX1 and MED1/Mediator are of functional importance for both gene-specific transcriptional activation and maintenance of E2A-PBX1–driven leukemia. The MED1 dependency for E2A-PBX1–mediated gene activation and leukemogenesis may provide a potential therapeutic opportunity by targeting MED1 in E2A-PBX1+ pre-B leukemia.

scholarly journals Domain-specific Gene Activation by Parathyroid Hormone in Osteoblastic ROS17/2.8 Cells

1996 ◽  
Vol 271 (36) ◽  
pp. 21870-21877 ◽  
Author(s):  
Angela Hollnagel ◽  
Dietmar Schröder ◽  
Gerhard Gross
Keyword(s):  
Parathyroid Hormone ◽  
Gene Activation ◽  
Specific Gene ◽  
Domain Specific

Non-autonomous regulation of a graded, PKA-mediated transcriptional activation signal for cell patterning

Development ◽  
1998 ◽  
Vol 125 (20) ◽  
pp. 3947-3954
Author(s):  
P. Balint-Kurti ◽  
G.T. Ginsburg ◽  
J. Liu ◽  
A.R. Kimmel
Keyword(s):  
Transcriptional Activation ◽  
Leucine Zipper ◽  
Gene Activation ◽  
Distal Segment ◽  
Dominant Negative ◽  
Regulatory Subunit ◽  
Specific Gene ◽  
Differentiated Cells ◽  
Extracellular Signal ◽  
Dependent Protein

The pseudoplasmodium or migrating slug of Dictyostelium is composed of non-terminally differentiated cells, organized along an anteroposterior axis. Cells in the anterior region of the slug define the prestalk compartment, whereas most of the posterior zone consists of prespore cells. We now present evidence that the cAMP-dependent protein kinase (PKA) and the RING domain/leucine zipper protein rZIP interact genetically to mediate a transcriptional activation gradient that regulates the differentiation of prespore cells within the posterior compartment of the slug. PKA is absolutely required for prespore differentiation. In contrast, rZIP negatively regulates prespore patterning; rzpA- cells, which lack rZIP, have reduced prestalk differentiation and a corresponding increase in prespore-specific gene expression. Using cell-specific markers and chimaeras of wild-type and rzpA- cells, we show that rZIP functions non-autonomously to establish a graded, prespore gene activation signal but autonomously to localize prespore expression. Overexpression of either the catalytic subunit or a dominant-negative regulatory subunit of PKA further demonstrates that PKA lies within the intracellular pathway that mediates the extracellular signal and regulates prespore patterning. Finally, we show that a 5′-distal segment within a prespore promoter that is responsive to a graded signal is also sensitive to PKA and rZIP, indicating that it acts directly at the level of prespore-specific gene transcription for regulation.

The nuclear lamina and heterochromatin: a complex relationship

2011 ◽  
Vol 39 (6) ◽  
pp. 1705-1709 ◽  
Author(s):  
Erin M. Bank ◽  
Yosef Gruenbaum
Keyword(s):  
Nuclear Periphery ◽  
Gene Activation ◽  
Nuclear Lamina ◽  
Current Evidence ◽  
Specific Gene ◽  
Nuclear Interior ◽  
Gene Retention ◽  
Gene Positioning ◽  
Review Current ◽  
Active Genes

In metazoan cells, the heterochromatin is generally localized at the nuclear periphery, whereas active genes are preferentially found in the nuclear interior. In the present paper, we review current evidence showing that components of the nuclear lamina interact directly with heterochromatin, which implicates the nuclear lamina in a mechanism of specific gene retention at the nuclear periphery and release to the nuclear interior upon gene activation. We also discuss recent data showing that mutations in lamin proteins affect gene positioning and expression, providing a potential mechanism for how these mutations lead to tissue-specific diseases.

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