Chromatin architecture is a flexible foundation for gene expression

2021 ◽  
Author(s):  
Tom Misteli ◽  
Elizabeth H. Finn
Keyword(s):  
Gene Expression ◽  
Chromatin Architecture ◽  
Flexible Foundation

scholarly journals Epigenomic landscape of enhancer elements during Hydra head organizer formation

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Puli Chandramouli Reddy ◽  
Akhila Gungi ◽  
Suyog Ubhe ◽  
Sanjeev Galande
Keyword(s):  
Gene Expression ◽  
Wnt Signaling ◽  
Histone Modifications ◽  
Specific Inhibitor ◽  
Regulatory Elements ◽  
The Body ◽  
Luciferase Reporter ◽  
Dependent Manner ◽  
Chromatin Architecture ◽  
Ectopic Activation

Abstract Background Axis patterning during development is accompanied by large-scale gene expression changes. These are brought about by changes in the histone modifications leading to dynamic alterations in chromatin architecture. The cis regulatory DNA elements also play an important role towards modulating gene expression in a context-dependent manner. Hydra belongs to the phylum Cnidaria where the first asymmetry in the body plan was observed and the oral-aboral axis originated. Wnt signaling has been shown to determine the head organizer function in the basal metazoan Hydra. Results To gain insights into the evolution of cis regulatory elements and associated chromatin signatures, we ectopically activated the Wnt signaling pathway in Hydra and monitored the genome-wide alterations in key histone modifications. Motif analysis of putative intergenic enhancer elements from Hydra revealed the conservation of bilaterian cis regulatory elements that play critical roles in development. Differentially regulated enhancer elements were identified upon ectopic activation of Wnt signaling and found to regulate many head organizer specific genes. Enhancer activity of many of the identified cis regulatory elements was confirmed by luciferase reporter assay. Quantitative chromatin immunoprecipitation analysis upon activation of Wnt signaling further confirmed the enrichment of H3K27ac on the enhancer elements of Hv_Wnt5a, Hv_Wnt11 and head organizer genes Hv_Bra1, CnGsc and Hv_Pitx1. Additionally, perturbation of the putative H3K27me3 eraser activity using a specific inhibitor affected the ectopic activation of Wnt signaling indicating the importance of the dynamic changes in the H3K27 modifications towards regulation of the genes involved in the head organizer activity. Conclusions The activation-associated histone marks H3K4me3, H3K27ac and H3K9ac mark chromatin in a similar manner as seen in bilaterians. We identified intergenic cis regulatory elements which harbor sites for key transcription factors involved in developmental processes. Differentially regulated enhancers exhibited motifs for many zinc-finger, T-box and ETS related TFs whose homologs have a head specific expression in Hydra and could be a part of the pioneer TF network in the patterning of the head. The ability to differentially modify the H3K27 residue is critical for the patterning of Hydra axis revealing a dynamic acetylation/methylation switch to regulate gene expression and chromatin architecture.

Abstract 1006: Non-linear relationship between estradiol-regulated changes in chromatin architecture and gene expression

2019 ◽  
Author(s):  
Taylor M. Parker ◽  
Duojiao Chen ◽  
Poornima Bhat-Nakshatri ◽  
Xiaona Chu ◽  
Yunlong Liu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Linear Relationship ◽  
Chromatin Architecture ◽  
Non Linear

scholarly journals The New Frontier of Functional Genomics: From Chromatin Architecture and Noncoding RNAs to Therapeutic Targets

2020 ◽  
Vol 25 (6) ◽  
pp. 568-580
Author(s):  
Natali Papanicolaou ◽  
Alessandro Bonetti
Keyword(s):  
Gene Expression ◽  
Association Studies ◽  
Noncoding Rnas ◽  
Regulatory Elements ◽  
Long Noncoding Rnas ◽  
Human Diseases ◽  
Genome Wide Association Studies ◽  
Complex Disorders ◽  
Chromatin Architecture ◽  
Common Diseases

Common diseases are complex, multifactorial disorders whose pathogenesis is influenced by the interplay of genetic predisposition and environmental factors. Genome-wide association studies have interrogated genetic polymorphisms across genomes of individuals to test associations between genotype and susceptibility to specific disorders, providing insights into the genetic architecture of several complex disorders. However, genetic variants associated with the susceptibility to common diseases are often located in noncoding regions of the genome, such as tissue-specific enhancers or long noncoding RNAs, suggesting that regulatory elements might play a relevant role in human diseases. Enhancers are cis-regulatory genomic sequences that act in concert with promoters to regulate gene expression in a precise spatiotemporal manner. They can be located at a considerable distance from their cognate target promoters, increasing the difficulty of their identification. Genomes are organized in domains of chromatin folding, namely topologically associating domains (TADs). Identification of enhancer–promoter interactions within TADs has revealed principles of cell-type specificity across several organisms and tissues. The vast majority of mammalian genomes are pervasively transcribed, accounting for a previously unappreciated complexity of the noncoding RNA fraction. Particularly, long noncoding RNAs have emerged as key players for the establishment of chromatin architecture and regulation of gene expression. In this perspective, we describe the new advances in the fields of transcriptomics and genome organization, focusing on the role of noncoding genomic variants in the predisposition of common diseases. Finally, we propose a new framework for the identification of the next generation of pharmacological targets for common human diseases.

scholarly journals Structure of the yeast Swi/Snf complex in a nucleosome free state

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Chengcheng Wang ◽  
Zhouyan Guo ◽  
Xiechao Zhan ◽  
Fenghua Yang ◽  
Mingxuan Wu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Saccharomyces Cerevisiae ◽  
Structural Features ◽  
Free State ◽  
Chromatin Remodelers ◽  
Chromatin Architecture ◽  
And Function ◽  
Base Module

Abstract SWI/SNF remodelers play a key role in regulating chromatin architecture and gene expression. Here, we report the cryo-EM structure of the Saccharomyces cerevisiae Swi/Snf complex in a nucleosome-free state. The structure consists of a stable triangular base module and a flexible Arp module. The conserved subunits Swi1 and Swi3 form the backbone of the complex and closely interact with other components. Snf6, which is specific for yeast Swi/Snf complex, stabilizes the binding of the ATPase-containing subunit Snf2 to the base module. Comparison of the yeast Swi/Snf and RSC complexes reveals conserved structural features that govern the assembly and function of these two subfamilies of chromatin remodelers. Our findings complement those from recent structures of the yeast and human chromatin remodelers and provide further insights into the assembly and function of the SWI/SNF remodelers.

scholarly journals Mediator and cohesin connect gene expression and chromatin architecture

Nature ◽  
2010 ◽  
Vol 467 (7314) ◽  
pp. 430-435 ◽  
Author(s):  
Michael H. Kagey ◽  
Jamie J. Newman ◽  
Steve Bilodeau ◽  
Ye Zhan ◽  
David A. Orlando ◽  
...  
Keyword(s):  
Gene Expression ◽  
Chromatin Architecture

scholarly journals Role of Chromatin Architecture in Plant Stress Responses: An Update

2021 ◽  
Vol 11 ◽  
Author(s):  
Sneha Lata Bhadouriya ◽  
Sandhya Mehrotra ◽  
Mahesh K. Basantani ◽  
Gary J. Loake ◽  
Rajesh Mehrotra
Keyword(s):  
Gene Expression ◽  
Stress Responses ◽  
Plant Stress ◽  
Stress Conditions ◽  
Current Evidence ◽  
Specific Gene ◽  
Functional Connection ◽  
Stress Memory ◽  
Chromatin Architecture

Sessile plants possess an assembly of signaling pathways that perceive and transmit environmental signals, ultimately resulting in transcriptional reprogramming. Histone is a key feature of chromatin structure. Numerous histone-modifying proteins act under different environmental stress conditions to help modulate gene expression. DNA methylation and histone modification are crucial for genome reprogramming for tissue-specific gene expression and global gene silencing. Different classes of chromatin remodelers including SWI/SNF, ISWI, INO80, and CHD are reported to act upon chromatin in different organisms, under diverse stresses, to convert chromatin from a transcriptionally inactive to a transcriptionally active state. The architecture of chromatin at a given promoter is crucial for determining the transcriptional readout. Further, the connection between somatic memory and chromatin modifications may suggest a mechanistic basis for a stress memory. Studies have suggested that there is a functional connection between changes in nuclear organization and stress conditions. In this review, we discuss the role of chromatin architecture in different stress responses and the current evidence on somatic, intergenerational, and transgenerational stress memory.

98 HETEROCHROMATIN REPROGRAMMING IN MOUSE EARLY DEVELOPMENT

2009 ◽  
Vol 21 (1) ◽  
pp. 149
Author(s):  
T. Wongtawan ◽  
J. Taylor ◽  
I. Wilmut ◽  
S. Pennings
Keyword(s):  
Gene Expression ◽  
Early Development ◽  
Nuclear Transfer ◽  
Technical Assistance ◽  
Es Cells ◽  
Cell Nuclei ◽  
Mouse Development ◽  
Fluorescent Intensity ◽  
Chromatin Architecture ◽  
Somatic Nuclear Transfer

Heterochromatin is essential for epigenetic gene silencing and nuclear chromatin architecture. Early mouse development is accompanied by dynamic epigenetic changes and heterochromatin restructuring in the cell nuclei of cleavage stage embryos. We have previously shown that disruption of heterochromatin markers such as DNA methylation following somatic nuclear transfer causes developmental failure (Beaujean N et al. 2004 Biol. Reprod. 71, 185–193). The aim of the present study was to investigate the transitions and maturation of heterochromatin during normal development to improve nuclear reprogramming technology and understand developmental abnormalities caused by epigenetic alterations in somatic nuclear transfer and assisted reproductive procedures. Mouse pre- and post-implantation embryos and ES cells from B6CBAF1 mice were used in experiments employing the following methodologies. Embryos and ES cells were stained by immunofluorescence to detect heterochromatin proteins and epigenetic markers. Images were captured using laser confocal microscopy. Relative quantification of fluorescent intensity was performed using Zeiss LSM-meta and WCIF-ImageJ software. mRNA of Histone methyltransferase (HMTase), suv39h, suv420h, ehmt, eset, and demethyltransferase (DHMTase), jmjd1a, jmjd2a, jmjd2c were quantified by real-time PCR. siRNA and specific inhibitors were used to study the function of suv39h, ehmt2, jmjd2c genes that may be responsible for heterochromatin reprogramming. Our results demonstrated that H3K9me3, H3K9me2, H4K20me2, H4K20me3, HP1α and HP1β are reprogrammed during early development. The gene expression results showed the dynamic and temporal gene expression of HMTases and DHMTase during development. Inhibition of Ehmt2 and jmjd2c caused preimplantation developmental arrest. Furthermore, we found chromatin modification differences in the heterochromatin of ES cells, ICM and epiblast. We conclude that heterochromatin reprogramming might be essential for development because it may contribute to chromatin architecture, thus influencing gene expression. HMTases and DHTMases could be implicated in the mechanism of heterochromatin reprogramming. It is possible that Ehmt2 and jmjd2c play an important role in preimplantation development by modifying chromatin globally and at the local gene level. This work was supported by a The Royal Thai Studentship. We acknowledge the contributions of technical assistance from T. O’Connor, B. Wongtawan and P. Travers.

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