Chromatin landscape signals differentially dictate the activities of mSWI/SNF family complexes

Science ◽  
2021 ◽  
Vol 373 (6552) ◽  
pp. 306-315
Author(s):  
Nazar Mashtalir ◽  
Hai T. Dao ◽  
Akshay Sankar ◽  
Hengyuan Liu ◽  
Aaron J. Corin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Histone Modification ◽  
Adenosine Triphosphate ◽  
Chromatin Remodelers ◽  
Chromatin States ◽  
Constituent Assembly ◽  
Chromatin Interactions ◽  
Specific Effects ◽  
Genomic Architecture ◽  
Nucleosome Binding

Mammalian SWI/SNF (mSWI/SNF) adenosine triphosphate–dependent chromatin remodelers modulate genomic architecture and gene expression and are frequently mutated in disease. However, the specific chromatin features that govern their nucleosome binding and remodeling activities remain unknown. We subjected endogenously purified mSWI/SNF complexes and their constituent assembly modules to a diverse library of DNA-barcoded mononucleosomes, performing more than 25,000 binding and remodeling measurements. Here, we define histone modification-, variant-, and mutation-specific effects, alone and in combination, on mSWI/SNF activities and chromatin interactions. Further, we identify the combinatorial contributions of complex module components, reader domains, and nucleosome engagement properties to the localization of complexes to selectively permissive chromatin states. These findings uncover principles that shape the genomic binding and activity of a major chromatin remodeler complex family.

scholarly journals Publisher Correction: Exogenously overexpressed intronic long noncoding RNAs activate host gene expression by affecting histone modification in Arabidopsis

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Zhang-Wei Liu ◽  
Nan Zhao ◽  
Yin-Na Su ◽  
Shan-Shan Chen ◽  
Xin-Jian He
Keyword(s):  
Gene Expression ◽  
Histone Modification ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Host Gene ◽  
Host Gene Expression

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

scholarly journals Glucocorticoid receptor wields chromatin interactions to tune transcription for cytoskeleton stabilization in podocytes

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Hong Wang ◽  
Aiping Duan ◽  
Jing Zhang ◽  
Qi Wang ◽  
Yuexian Xing ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Glucocorticoid Receptor ◽  
Protective Effect ◽  
Histone Modification ◽  
Regulatory Networks ◽  
Target Gene ◽  
Regulatory Elements ◽  
Chromatin Interactions ◽  
Super Enhancer

AbstractElucidating transcription mediated by the glucocorticoid receptor (GR) is crucial for understanding the role of glucocorticoids (GCs) in the treatment of diseases. Podocyte is a useful model for studying GR regulation because GCs are the primary medication for podocytopathy. In this study, we integrated data from transcriptome, transcription factor binding, histone modification, and genome topology. Our data reveals that the GR binds and activates selective regulatory elements in podocyte. The 3D interactome captured by HiChIP facilitates the identification of remote targets of GR. We found that GR in podocyte is enriched at transcriptional interaction hubs and super-enhancers. We further demonstrate that the target gene of the top GR-associated super-enhancer is indispensable to the effective functioning of GC in podocyte. Our findings provided insights into the mechanisms underlying the protective effect of GCs on podocyte, and demonstrate the importance of considering transcriptional interactions in order to fine-map regulatory networks of GR.

scholarly journals ARID2 Chromatin Remodeler in Hepatocellular Carcinoma

Cells ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 2152
Author(s):  
Robin Loesch ◽  
Linda Chenane ◽  
Sabine Colnot
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Associated Factors ◽  
Regulation Of Gene Expression ◽  
Specific Gene ◽  
Chromatin Remodeler ◽  
Chromatin Remodelers ◽  
Genes Encoding ◽  
Gene Alterations

Chromatin remodelers are found highly mutated in cancer including hepatocellular carcinoma. These mutations frequently occur in ARID (AT-rich Interactive Domain) genes, encoding subunits of the ATP-dependent SWI/SNF remodelers. The increasingly prevalent complexity that surrounds the functions and specificities of the highly modular BAF (BG1/BRM-associated factors) and PBAF (polybromo-associated BAF) complexes, including ARID1A/B or ARID2, is baffling. The involvement of the SWI/SNF complexes in diverse tissues and processes, and especially in the regulation of gene expression, multiplies the specific outcomes of specific gene alterations. A better understanding of the molecular consequences of specific mutations impairing chromatin remodelers is needed. In this review, we summarize what we know about the tumor-modulating properties of ARID2 in hepatocellular carcinoma.

scholarly journals The aquaglyceroporin AQP9 contributes to the sex-specific effects of in utero arsenic exposure on placental gene expression

2017 ◽  
Vol 16 (1) ◽  
Author(s):  
Emily F. Winterbottom ◽  
Devin C. Koestler ◽  
Dennis Liang Fei ◽  
Eric Wika ◽  
Anthony J. Capobianco ◽  
...  
Keyword(s):  
Gene Expression ◽  
Arsenic Exposure ◽  
In Utero ◽  
Specific Effects

scholarly journals Sex-specific longitudinal association of DNA methylation with lung function

2021 ◽  
pp. 00127-2021
Author(s):  
Shadia Khan Sunny ◽  
Hongmei Zhang ◽  
Caroline L. Relton ◽  
Susan Ring ◽  
Latha Kadalayil ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lung Function ◽  
Mixed Models ◽  
Enrichment Analysis ◽  
Expression Data ◽  
Specific Effects ◽  
Parents And Children ◽  
Longitudinal Association ◽  
Males And Females ◽  
Avon Longitudinal Study

Investigating whether DNA-M at an earlier age is associated with lung function at a later age and whether this relationship differs by sex could enable prediction of future lung function deficit.A training/testing-based technique was used to screen 402 714 cytosine-phosphate-guanine dinucleotide sites (CpGs) to assess the longitudinal association of blood-based DNA-M at ages 10 and 18-years with lung function at 18 and 26-years, respectively, in the Isle of Wight birth cohort (IOWBC). Multivariable linear mixed models were applied to the CpGs that passed screening. To detect differentially methylated regions (DMRs), DMR enrichment analysis was conducted. Findings were further examined in the Avon Longitudinal Study of Parents and Children (ALSPAC). Biological relevance of the identified CpGs was assessed utilizing gene expression data.DNA-M at 8 CpGs (FEV1: 5 and FEV1/FVC: 3 CpGs) at an earlier age was associated with lung function at a later age regardless of sex, while at 13 CpGs (FVC: 5, FEV1:3, and FEV1/FVC: 5 CpGs), the associations were sex-specific (pFDR<0.05) in IOWBC with consistent directions of association in ALSPAC (IOWBC-ALSPAC consistent CpGs). cg16582803 (WNT10A) and cg14083603 (ZGPAT) were replicated in ALSPAC for main and sex-specific effects, respectively. Among IOWBC-ALSPAC consistent CpGs, DNA-M at cg01376079 (SSH3) and cg07557690 (TGFBR3) was associated with gene expression both longitudinally and cross-sectionally. In total, 57 and 170 DMRs were linked to lung function longitudinally in males and females, respectively.CpGs showing longitudinal associations with lung function have the potential to serve as candidate markers in future studies on lung function deficit prediction.

scholarly journals Function of cofactor Akirin2 in the regulation of gene expression in model human Caucasian neutrophil-like HL60 cells

2021 ◽  
Author(s):  
Sara Artigas-Jerónimo ◽  
Margarita Villar ◽  
Agustín Estrada-Peña ◽  
Adrián Velázquez-Campoy ◽  
Pilar Alberdi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Neural Development ◽  
Transcriptional Activation ◽  
Regulation Of Gene Expression ◽  
Regulatory Function ◽  
Biological Processes ◽  
Protein Targets ◽  
Chromatin Remodelers ◽  
Hl60 Cells ◽  
Associated Proteins

The Akirin family of transcription cofactors are involved throughout the metazoan in the regulation of different biological processes such as immunity, interdigital regression, muscle and neural development. Akirin do not have catalytic or DNA-binding capability and exert its regulatory function primarily through interacting proteins such as transcription factors, chromatin remodelers, and RNA-associated proteins. In this study, we focused on the human Akirin2 regulome and interactome in neutrophil-like model human Caucasian promyelocytic leukemia HL60 cells. Our hypothesis is that metazoan evolved to have Akirin2 functional complements and different Akirin2-mediated mechanisms for the regulation of gene expression. To address this hypothesis, experiments were conducted using transcriptomics, proteomics and systems biology approaches in akirin2 knockdown and wildtype HL60 cells to characterize Akirin2 gene/protein targets, functional complements and to provide evidence of different mechanisms that may be involved in Akirin2-mediated regulation of gene expression. The results revealed Akirin2 gene/protein targets in multiple biological processes with higher representation of immunity and identified immune response genes as candidate Akirin2 functional complements. In addition to linking chromatin remodelers with transcriptional activation, Akirin2 also interacts with histone H3.1 for regulation of gene expression.

scholarly journals Phosphorylation-dependent mitotic SUMOylation drives nuclear envelope–chromatin interactions

2021 ◽  
Vol 220 (12) ◽  
Author(s):  
Christopher Ptak ◽  
Natasha O. Saik ◽  
Ashwini Premashankar ◽  
Diego L. Lapetina ◽  
John D. Aitchison ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nuclear Envelope ◽  
Spatial Organization ◽  
G1 Phase ◽  
Nuclear Pore ◽  
Nuclear Pore Complexes ◽  
Chromatin Binding ◽  
Chromatin Interactions ◽  
Sumo Ligase ◽  
Pore Complexes

In eukaryotes, chromatin binding to the inner nuclear membrane (INM) and nuclear pore complexes (NPCs) contributes to spatial organization of the genome and epigenetic programs important for gene expression. In mitosis, chromatin–nuclear envelope (NE) interactions are lost and then formed again as sister chromosomes segregate to postmitotic nuclei. Investigating these processes in S. cerevisiae, we identified temporally and spatially controlled phosphorylation-dependent SUMOylation events that positively regulate postmetaphase chromatin association with the NE. Our work establishes a phosphorylation-mediated targeting mechanism of the SUMO ligase Siz2 to the INM during mitosis, where Siz2 binds to and SUMOylates the VAP protein Scs2. The recruitment of Siz2 through Scs2 is further responsible for a wave of SUMOylation along the INM that supports the assembly and anchorage of subtelomeric chromatin at the INM and localization of an active gene (INO1) to NPCs during the later stages of mitosis and into G1-phase.

scholarly journals A histone modification identifies a DNA element controllingsloBK channel gene expression in muscle

2015 ◽  
Vol 29 (2-3) ◽  
pp. 124-134 ◽  
Author(s):  
Xiaolei Li ◽  
Alfredo Ghezzi ◽  
Harish R. Krishnan ◽  
Jascha B. Pohl ◽  
Arun Y. Bohm ◽  
...  
Keyword(s):  
Gene Expression ◽  
Histone Modification ◽  
Channel Gene
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