scholarly journals β-actin dependent chromatin remodeling mediates compartment level changes in 3D genome architecture

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Syed Raza Mahmood ◽  
Xin Xie ◽  
Nadine Hosny El Said ◽  
Tomas Venit ◽  
Kristin C. Gunsalus ◽  
...  

Abstractβ-actin is a crucial component of several chromatin remodeling complexes that control chromatin structure and accessibility. The mammalian Brahma-associated factor (BAF) is one such complex that plays essential roles in development and differentiation by regulating the chromatin state of critical genes and opposing the repressive activity of polycomb repressive complexes (PRCs). While previous work has shown that β-actin loss can lead to extensive changes in gene expression and heterochromatin organization, it is not known if changes in β-actin levels can directly influence chromatin remodeling activities of BAF and polycomb proteins. Here we conduct a comprehensive genomic analysis of β-actin knockout mouse embryonic fibroblasts (MEFs) using ATAC-Seq, HiC-seq, RNA-Seq and ChIP-Seq of various epigenetic marks. We demonstrate that β-actin levels can induce changes in chromatin structure by affecting the complex interplay between chromatin remodelers such as BAF/BRG1 and EZH2. Our results show that changes in β-actin levels and associated chromatin remodeling activities can not only impact local chromatin accessibility but also induce reversible changes in 3D genome architecture. Our findings reveal that β-actin-dependent chromatin remodeling plays a role in shaping the chromatin landscape and influences the regulation of genes involved in development and differentiation.

2020 ◽  
Author(s):  
Syed Raza Mahmood ◽  
Xin Xie ◽  
Nadine Hosny El Said ◽  
Kristin C. Gunsalus ◽  
Piergiorgio Percipalle

Abstractβ-actin is a crucial component of several chromatin remodeling complexes that control chromatin structure and accessibility. The mammalian Brahma-associated factor (BAF) is one such complex that plays essential roles in development and differentiation by regulating the chromatin state of critical genes and opposing the repressive activity of polycomb repressive complexes (PRCs). While previous work has shown that β-actin loss can lead to extensive changes in gene expression and heterochromatin organization, it is not known if changes in β-actin levels can directly influence chromatin remodeling activities of BAF and polycomb proteins. Here we conduct a comprehensive genomic analysis of β-actin knockout mouse embryonic fibroblasts (MEFs) using ATAC-Seq, HiC-seq, RNA-Seq and ChIP-Seq of various epigenetic marks. We demonstrate that β-actin levels can affect the complex interplay between chromatin remodelers such as BAF/BRG1 and EZH2 in a dosage-dependent manner. Our results show that changes in β-actin levels and associated chromatin remodeling activities can not only impact local chromatin accessibility but also induce reversible changes in 3D genome architecture. Our findings support a novel role for β-actin-dependent chromatin remodeling in shaping the chromatin landscape and regulating genes involved in development and differentiation.


2010 ◽  
Vol 30 (13) ◽  
pp. 3176-3186 ◽  
Author(s):  
Chandrashekara Mallappa ◽  
Brian T. Nasipak ◽  
Letitiah Etheridge ◽  
Elliot J. Androphy ◽  
Stephen N. Jones ◽  
...  

ABSTRACT Knockdown of the Brg1 ATPase subunit of SWI/SNF chromatin remodeling enzymes in developing zebrafish caused stunted tail formation and altered sarcomeric actin organization, which phenocopies the loss of the microRNA processing enzyme Dicer, or the knockdown of myogenic microRNAs. Furthermore, myogenic microRNA expression and differentiation was blocked in Brg1 conditional myoblasts differentiated ex vivo. The binding of Brg1 upstream of myogenic microRNA sequences correlated with MyoD binding and accessible chromatin structure in satellite cells and myofibers, and it was required for chromatin accessibility and microRNA expression in a tissue culture model for myogenesis. The results implicate ATP-dependent chromatin remodelers in myogenic microRNA gene regulation.


2011 ◽  
Vol 89 (5) ◽  
pp. 435-444 ◽  
Author(s):  
Nathalie G. Bérubé

The regulation of genome architecture is essential for a variety of fundamental cellular phenomena that underlie the complex orchestration of mammalian development. The ATP-dependent chromatin remodeling protein ATRX is emerging as a key regulatory component of nucleosomal dynamics and higher order chromatin conformation. Here we provide an overview of the role of ATRX at chromatin and during development, and discuss recent studies exposing a repertoire of ATRX functions at heterochromatin, in gene regulation, and during mitosis and meiosis. Exciting new progress on several fronts suggest that ATRX operates in histone variant deposition and in the modulation of higher order chromatin structure. Not surprisingly, dysfunction or absence of ATRX protein has devastating consequences on embryonic development and leads to human disease.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Hyelim Jo ◽  
Taemook Kim ◽  
Yujin Chun ◽  
Inkyung Jung ◽  
Daeyoup Lee

AbstractWe herein employ in situ Hi-C with an auxin-inducible degron (AID) system to examine the effect of chromatin remodeling on 3D genome organization in yeast. Eight selected ATP-dependent chromatin remodelers representing various subfamilies contribute to 3D genome organization differently. Among the studied remodelers, the temporary depletions of Chd1p, Swr1p, and Sth1p (a catalytic subunit of the Remodeling the Structure of Chromatin [RSC] complex) cause the most significant defects in intra-chromosomal contacts, and the regulatory roles of these three remodelers in 3D genome organization differ depending on the chromosomal context and cell cycle stage. Furthermore, even though Chd1p and Isw1p are known to share functional similarities/redundancies, their depletions lead to distinct effects on 3D structures. The RSC and cohesin complexes also differentially modulate 3D genome organization within chromosome arm regions, whereas RSC appears to support the function of cohesin in centromeric clustering at G2 phase. Our work suggests that the ATP-dependent chromatin remodelers control the 3D genome organization of yeast through their chromatin-remodeling activities.


BioEssays ◽  
2019 ◽  
Vol 41 (3) ◽  
pp. 1800222 ◽  
Author(s):  
Vincent Loubiere ◽  
Anne-Marie Martinez ◽  
Giacomo Cavalli

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Karolina Stępniak ◽  
Magdalena A. Machnicka ◽  
Jakub Mieczkowski ◽  
Anna Macioszek ◽  
Bartosz Wojtaś ◽  
...  

AbstractChromatin structure and accessibility, and combinatorial binding of transcription factors to regulatory elements in genomic DNA control transcription. Genetic variations in genes encoding histones, epigenetics-related enzymes or modifiers affect chromatin structure/dynamics and result in alterations in gene expression contributing to cancer development or progression. Gliomas are brain tumors frequently associated with epigenetics-related gene deregulation. We perform whole-genome mapping of chromatin accessibility, histone modifications, DNA methylation patterns and transcriptome analysis simultaneously in multiple tumor samples to unravel epigenetic dysfunctions driving gliomagenesis. Based on the results of the integrative analysis of the acquired profiles, we create an atlas of active enhancers and promoters in benign and malignant gliomas. We explore these elements and intersect with Hi-C data to uncover molecular mechanisms instructing gene expression in gliomas.


2021 ◽  
Vol 7 (1) ◽  
pp. 37
Author(s):  
Mohammad N. Qasim ◽  
Ashley Valle Arevalo ◽  
Clarissa J. Nobile ◽  
Aaron D. Hernday

Candida albicans, a diploid polymorphic fungus, has evolved a unique heritable epigenetic program that enables reversible phenotypic switching between two cell types, referred to as “white” and “opaque”. These cell types are established and maintained by distinct transcriptional programs that lead to differences in metabolic preferences, mating competencies, cellular morphologies, responses to environmental signals, interactions with the host innate immune system, and expression of approximately 20% of genes in the genome. Transcription factors (defined as sequence specific DNA-binding proteins) that regulate the establishment and heritable maintenance of the white and opaque cell types have been a primary focus of investigation in the field; however, other factors that impact chromatin accessibility, such as histone modifying enzymes, chromatin remodelers, and histone chaperone complexes, also modulate the dynamics of the white-opaque switch and have been much less studied to date. Overall, the white-opaque switch represents an attractive and relatively “simple” model system for understanding the logic and regulatory mechanisms by which heritable cell fate decisions are determined in higher eukaryotes. Here we review recent discoveries on the roles of chromatin accessibility in regulating the C. albicans white-opaque phenotypic switch.


2020 ◽  
Vol 22 (1) ◽  
pp. 76
Author(s):  
Aaron Morgan ◽  
Sarah LeGresley ◽  
Christopher Fischer

The packaging of the eukaryotic genome into chromatin regulates the storage of genetic information, including the access of the cell’s DNA metabolism machinery. Indeed, since the processes of DNA replication, translation, and repair require access to the underlying DNA, several mechanisms, both active and passive, have evolved by which chromatin structure can be regulated and modified. One mechanism relies upon the function of chromatin remodeling enzymes which couple the free energy obtained from the binding and hydrolysis of ATP to the mechanical work of repositioning and rearranging nucleosomes. Here, we review recent work on the nucleosome mobilization activity of this essential family of molecular machines.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Diana Buitrago ◽  
Mireia Labrador ◽  
Juan Pablo Arcon ◽  
Rafael Lema ◽  
Oscar Flores ◽  
...  

AbstractDetermining the effect of DNA methylation on chromatin structure and function in higher organisms is challenging due to the extreme complexity of epigenetic regulation. We studied a simpler model system, budding yeast, that lacks DNA methylation machinery making it a perfect model system to study the intrinsic role of DNA methylation in chromatin structure and function. We expressed the murine DNA methyltransferases in Saccharomyces cerevisiae and analyzed the correlation between DNA methylation, nucleosome positioning, gene expression and 3D genome organization. Despite lacking the machinery for positioning and reading methylation marks, induced DNA methylation follows a conserved pattern with low methylation levels at the 5’ end of the gene increasing gradually toward the 3’ end, with concentration of methylated DNA in linkers and nucleosome free regions, and with actively expressed genes showing low and high levels of methylation at transcription start and terminating sites respectively, mimicking the patterns seen in mammals. We also see that DNA methylation increases chromatin condensation in peri-centromeric regions, decreases overall DNA flexibility, and favors the heterochromatin state. Taken together, these results demonstrate that methylation intrinsically modulates chromatin structure and function even in the absence of cellular machinery evolved to recognize and process the methylation signal.


2018 ◽  
Vol 19 (12) ◽  
pp. 789-800 ◽  
Author(s):  
M. Jordan Rowley ◽  
Victor G. Corces

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