scholarly journals Hippocampal stimulation promotes intracellular Tip60 dynamics with concomitant genome reorganization and synaptic gene activation

2019 ◽  
Vol 101 ◽  
pp. 103412 ◽  
Author(s):  
Ashley Karnay ◽  
Bhanu Chandra Karisetty ◽  
Mariah Beaver ◽  
Felice Elefant
2021 ◽  
Author(s):  
Surabhi Chowdhary ◽  
Amoldeep S. Kainth ◽  
Sarah Paracha ◽  
David S. Gross ◽  
David Pincus

Mammalian developmental and disease-associated genes concentrate large quantities of the transcriptional machinery by forming membrane-less compartments known as transcriptional condensates. However, it is unknown whether these structures are evolutionarily conserved, capable of stress-inducible gene activation or involved in 3D genome reorganization. Here, we identify inducible transcriptional condensates in the yeast heat shock response (HSR). HSR condensates are biophysically dynamic spatiotemporal clusters of the sequence-specific transcription factor Heat shock factor 1 (Hsf1) with Mediator and RNA Pol II. Uniquely, HSR condensates drive the coalescence of multiple Hsf1 target genes, even those located on different chromosomes. Binding of the chaperone Hsp70 to a site on Hsf1 represses clustering, while an intrinsically disordered region on Hsf1 promotes condensate formation and intergenic interactions. Mutation of both Hsf1 determinants reprograms HSR condensates to become mammalian-like: constitutively active without intergenic coalescence. These results suggest that transcriptional condensates are ancient and flexible compartments of eukaryotic gene control.


Author(s):  
Gregory J. Czarnota

Chromatin structure at the fundamental level of the nucleosome is important in vital cellular processes. Recent biochemical and genetic analyses show that nucleosome structure and structural changes are very active participants in gene expression, facilitating or inhibiting transcription and reflecting the physiological state of the cell. Structural states and transitions for this macromolecular complex, composed of DNA wound about a heterotypic octamer of variously modified histone proteins, have been measured by physico-chemical techniques and by enzyme-accessibility and are recognized to occur with various post-translational modifications, gene activation, transformation and with ionic-environment. In spite of studies which indicate various forms of nucleosome structure, all current x-ray and neutron diffraction studies have consistently resulted in only one structure, suggestive of a static conformation. In contrast, two-dimensional electron microscopy studies and three-dimensional reconstruction techniques have yielded different structures. These fundamental differences between EM and other ultrastructural studies have created a long standing quandary, which I have addressed and resolved using spectroscopic electron microscopy and statistical analyses of nucleosome images in a study of nucleosome structure with ionic environment.


1972 ◽  
Vol 71 (2_Suppla) ◽  
pp. S346-S368 ◽  
Author(s):  
Roger W. Turkington ◽  
Nobuyuki Kadohama

ABSTRACT Hormonal activation of gene transcription has been studied in a model system, the mouse mammary gland in organ culture. Transcriptive activity is stimulated in mammary stem cells by insulin, and in mammary alveolar cells by prolactin and insulin. Studies on the template requirement for expression of the genes for milk proteins demonstrate that DNA methylation has an obligatory dependence upon DNA synthesis, but is otherwise independent from hormonal regulation of mammary cell differentiation. Incorporation of 5-bromo-2′deoxyuridine into DNA selectively inhibits expression of the genes for specific milk proteins. Undifferentiated mammary cells activate the synthesis of specific acidic nuclear proteins when stimulated by insulin. Several of these induced acidic nuclear proteins are undetectable in unstimulated undifferentiated cells, but appear to be characteristic components of the nuclei of differentiated cells. These results indicate that mammary cell differentiation is associated with a change in acidic nuclear proteins, and they provide evidence to support the concept that acidic nuclear proteins may be involved in the regulation of gene transcription and of mammary cell differentiation.


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