scholarly journals Ubiquitylated H2A.Z nucleosomes are associated with nuclear architectural proteins and global transcriptional silencing

2019 ◽  
Author(s):  
Marlee K. Ng ◽  
Ulrich Braunschweig ◽  
Benjamin J. Blencowe ◽  
Peter Cheung
Keyword(s):  
Gene Silencing ◽  
Transcriptional Repression ◽  
Transcriptional Silencing ◽  
Higher Order ◽  
Chromatin Organization ◽  
Post Translational Modification ◽  
H3k4 Methylation ◽  
Genome Wide ◽  
Architectural Proteins ◽  
Active Transcription

SummaryH2A.Z mono-ubiquitylation has been linked to transcriptional repression, but the mechanisms involved are not well understood. To address this, we developed a biotinylation-based approach to purify ubiquitylated H2A.Z (H2A.Zub) mononucleosomes for biochemical and genome-wide analyses. We observe that H2A.Zub nucleosomes are enriched for the repressive histone post-translational modification H3K27me3, but depleted of H3K4 methylation and other modifications associated with active transcription. ChIP-Seq analyses reveal that H2A.Zub-nucleosomes are enriched over non-expressed genes, and suggest that it is the relative ratio of ubiquitylated to non-ubiquitylated H2A.Z, rather than absolute presence or absence of H2A.Z ubiquitylation, that correlates with gene silencing. Finally, we observe that H2A.Zub-eniched mononucleosomes preferentially co-purify with transcriptional silencing factors as well as proteins involved in higher order chromatin organization such as CTCF and cohesin. Collectively, these results suggest an important role for H2A.Z ubiquitylation in mediating global transcriptional repression through its recruitment of silencing factors and nuclear architectural proteins.

scholarly journals XIST RNA: a window into the broader role of RNA in nuclear chromosome architecture

2017 ◽  
Vol 372 (1733) ◽  
pp. 20160360 ◽  
Author(s):  
K. M. Creamer ◽  
J. B. Lawrence
Keyword(s):  
X Chromosome ◽  
Chromatin Condensation ◽  
Higher Order ◽  
Chromosome Architecture ◽  
Genome Wide ◽  
Xist Rna ◽  
Architectural Proteins ◽  
Mary Lyon ◽  
Attachment Factor

XIST RNA triggers the transformation of an active X chromosome into a condensed, inactive Barr body and therefore provides a unique window into transitions of higher-order chromosome architecture. Despite recent progress, how XIST RNA localizes and interacts with the X chromosome remains poorly understood. Genetic engineering of XIST into a trisomic autosome demonstrates remarkable capacity of XIST RNA to localize and comprehensively silence that autosome. Thus, XIST does not require X chromosome-specific sequences but operates on mechanisms available genome-wide. Prior results suggested XIST localization is controlled by attachment to the insoluble nuclear scaffold. Our recent work affirms that scaffold attachment factor A (SAF-A) is involved in anchoring XIST , but argues against the view that SAF-A provides a unimolecular bridge between RNA and the chromosome. Rather, we suggest that a complex meshwork of architectural proteins interact with XIST RNA. Parallel work studying the territory of actively transcribed chromosomes suggests that repeat-rich RNA ‘coats’ euchromatin and may impact chromosome architecture in a manner opposite of XIST . A model is discussed whereby RNA may not just recruit histone modifications, but more directly impact higher-order chromatin condensation via interaction with architectural proteins of the nucleus. This article is part of the themed issue ‘X-chromosome inactivation: a tribute to Mary Lyon’.

Regulation of subtelomeric fungal secondary metabolite genes by H3K4me3 regulators CclA and KdmB

2020 ◽  
Author(s):  
Yonathan Lukito ◽  
T Chujo ◽  
TK Hale ◽  
W Mace ◽  
LJ Johnson ◽  
...  
Keyword(s):  
Secondary Metabolite ◽  
Transcriptional Activation ◽  
Transcriptional Repression ◽  
Target Genes ◽  
H3k4 Methylation ◽  
Genome Wide ◽  
H3k4me3 Mark ◽  
Transcriptional Changes ◽  
Histone H3k4 ◽  
A Site

© 2019 John Wiley & Sons Ltd Studies on the regulation of fungal secondary metabolism highlight the importance of histone H3K4 methylation regulators Set1, CclA (Ash2) and KdmB (KDM5), but it remains unclear whether these proteins act by direct modulation of H3K4me3 at the target genes. In filamentous fungi, secondary metabolite genes are frequently located near telomeres, a site where H3K4 methylation is thought to have a repressive role. Here we analyzed the role of CclA, KdmB and H3K4me3 in regulating the subtelomeric EAS and LTM cluster genes in Epichloë festucae. Depletion of H3K4me3 correlated with transcriptional activation of these genes in ΔcclA, similarly enrichment of H3K4me3 correlated with transcriptional repression of the genes in ΔkdmB which was accompanied by significant reduction in the levels of the agriculturally undesirable lolitrems. These transcriptional changes could only be explained by the alterations in H3K4me3 and not in the subtelomerically-important marks H3K9me3/K27me3. However, H3K4me3 changes in both mutants were not confined to these regions but occurred genome-wide, and at other subtelomeric loci there were inconsistent correlations between H3K4me3 enrichment and gene repression. Our study suggests that CclA and KdmB are crucial regulators of secondary metabolite genes, but these proteins likely act via means independent to, or in conjunction with the H3K4me3 mark.

scholarly journals Characterization of genome-wide enhancer-promoter interactions reveals co-expression of interacting genes and modes of higher order chromatin organization

Cell Research ◽  
2012 ◽  
Vol 22 (3) ◽  
pp. 490-503 ◽  
Author(s):  
Iouri Chepelev ◽  
Gang Wei ◽  
Dara Wangsa ◽  
Qingsong Tang ◽  
Keji Zhao
Keyword(s):  
Higher Order ◽  
Chromatin Organization ◽  
Genome Wide

scholarly journals Regulation of Sox8 through lncRNA Mrhl mediated chromatin looping in mouse spermatogonia

2021 ◽  
Author(s):  
Bhavana Kayyar ◽  
Anjhana C. Ravikkumar ◽  
Utsa Bhaduri ◽  
M.R.S Rao
Keyword(s):  
Transcription Factor ◽  
Transcriptional Repression ◽  
Regulation Of Transcription ◽  
Chromatin Loop ◽  
Gene Body ◽  
Chromatin Looping ◽  
Adult Mice ◽  
Architectural Proteins ◽  
Active Transcription ◽  
Silencer Element

AbstractSox8 is a developmentally important transcription factor that plays an important role in sex maintenance and fertility of adult mice. In the B-type spermatogonial cells, Sox8 is regulated by the lncRNA Mrhl in a p68-dependant manner under the control of the Wnt signalling pathway. The downregulation of Mrhl leads to the meiotic commitment of the spermatogonial cells in a Sox8-dependant manner. While the molecular players involved in the regulation of transcription at the Sox8 promoter have been worked out, our current study points to the involvement of the architectural proteins CTCF and cohesin in mediating a chromatin loop that brings the Sox8 promoter in contact with a silencer element present within the gene body in the presence of lncRNA Mrhl concomitant with transcriptional repression. Further, lncRNA Mrhl interacts with the Sox8 locus through the formation of a DNA:DNA:RNA triplex which is necessary for the recruitment of PRC2 to the locus. The downregulation of lncRNA Mrhl results in the promoter-silencer loop giving way to a promoter-enhancer loop. This active transcription associated chromatin loop is mediated by YY1 and brings the promoter in contact with the enhancer present downstream of the gene.

Regulation of subtelomeric fungal secondary metabolite genes by H3K4me3 regulators CclA and KdmB

2020 ◽  
Author(s):  
Yonathan Lukito ◽  
T Chujo ◽  
TK Hale ◽  
W Mace ◽  
LJ Johnson ◽  
...  
Keyword(s):  
Secondary Metabolite ◽  
Transcriptional Activation ◽  
Transcriptional Repression ◽  
Target Genes ◽  
H3k4 Methylation ◽  
Genome Wide ◽  
H3k4me3 Mark ◽  
Transcriptional Changes ◽  
Histone H3k4 ◽  
A Site

© 2019 John Wiley & Sons Ltd Studies on the regulation of fungal secondary metabolism highlight the importance of histone H3K4 methylation regulators Set1, CclA (Ash2) and KdmB (KDM5), but it remains unclear whether these proteins act by direct modulation of H3K4me3 at the target genes. In filamentous fungi, secondary metabolite genes are frequently located near telomeres, a site where H3K4 methylation is thought to have a repressive role. Here we analyzed the role of CclA, KdmB and H3K4me3 in regulating the subtelomeric EAS and LTM cluster genes in Epichloë festucae. Depletion of H3K4me3 correlated with transcriptional activation of these genes in ΔcclA, similarly enrichment of H3K4me3 correlated with transcriptional repression of the genes in ΔkdmB which was accompanied by significant reduction in the levels of the agriculturally undesirable lolitrems. These transcriptional changes could only be explained by the alterations in H3K4me3 and not in the subtelomerically-important marks H3K9me3/K27me3. However, H3K4me3 changes in both mutants were not confined to these regions but occurred genome-wide, and at other subtelomeric loci there were inconsistent correlations between H3K4me3 enrichment and gene repression. Our study suggests that CclA and KdmB are crucial regulators of secondary metabolite genes, but these proteins likely act via means independent to, or in conjunction with the H3K4me3 mark.

scholarly journals Restriction of Retrotransposon Mobilization inSchizosaccharomyces pombeby Transcriptional Silencing and Higher-Order Chromatin Organization

Genetics ◽  
2016 ◽  
Vol 203 (4) ◽  
pp. 1669-1678 ◽  
Author(s):  
Heather E. Murton ◽  
Patrick J. R. Grady ◽  
Tsun Ho Chan ◽  
Hugh P. Cam ◽  
Simon K. Whitehall
Keyword(s):  
Transcriptional Silencing ◽  
Higher Order ◽  
Chromatin Organization

scholarly journals The MBD7 complex promotes expression of methylated transgenes without significantly altering their methylation status

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Dongming Li ◽  
Ana Marie S Palanca ◽  
So Youn Won ◽  
Lei Gao ◽  
Ying Feng ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Arabidopsis Thaliana ◽  
Gene Silencing ◽  
Methylation Status ◽  
Transcriptional Silencing ◽  
Binding Domain ◽  
Number Of Factors ◽  
Genome Wide ◽  
Eukaryotic Organisms

DNA methylation is associated with gene silencing in eukaryotic organisms. Although pathways controlling the establishment, maintenance and removal of DNA methylation are known, relatively little is understood about how DNA methylation influences gene expression. Here we identified a METHYL-CpG-BINDING DOMAIN 7 (MBD7) complex in Arabidopsis thaliana that suppresses the transcriptional silencing of two LUCIFERASE (LUC) reporters via a mechanism that is largely downstream of DNA methylation. Although mutations in components of the MBD7 complex resulted in modest increases in DNA methylation concomitant with decreased LUC expression, we found that these hyper-methylation and gene expression phenotypes can be genetically uncoupled. This finding, along with genome-wide profiling experiments showing minimal changes in DNA methylation upon disruption of the MBD7 complex, places the MBD7 complex amongst a small number of factors acting downstream of DNA methylation. This complex, however, is unique as it functions to suppress, rather than enforce, DNA methylation-mediated gene silencing.

scholarly journals Dynamic histone acetylation in floral volatile synthesis and emission in petunia flowers

2021 ◽  
Author(s):  
Ryan M Patrick ◽  
Xing-Qi Huang ◽  
Natalia Dudareva ◽  
Ying Li
Keyword(s):  
Transcriptional Activation ◽  
Metabolic Pathways ◽  
Transcriptional Repression ◽  
Metabolic Networks ◽  
Underlying Mechanism ◽  
Expression Of Genes ◽  
Genome Wide ◽  
Chemical Inhibitors ◽  
Volatile Organic ◽  
Floral Volatile

Abstract Biosynthesis of secondary metabolites relies on primary metabolic pathways to provide precursors, energy, and cofactors, thus requiring coordinated regulation of primary and secondary metabolic networks. However, to date, it remains largely unknown how this coordination is achieved. Using Petunia hybrida flowers, which emit high levels of phenylpropanoid/benzenoid volatile organic compounds (VOCs), we uncovered genome-wide dynamic deposition of histone H3 lysine 9 acetylation (H3K9ac) during anthesis as an underlying mechanism to coordinate primary and secondary metabolic networks. The observed epigenome reprogramming is accompanied by transcriptional activation at gene loci involved in primary metabolic pathways that provide precursor phenylalanine, as well as secondary metabolic pathways to produce volatile compounds. We also observed transcriptional repression among genes involved in alternative phenylpropanoid branches that compete for metabolic precursors. We show that GNAT family histone acetyltransferase(s) (HATs) are required for the expression of genes involved in VOC biosynthesis and emission, by using chemical inhibitors of HATs, and by knocking down a specific HAT gene, ELP3, through transient RNAi. Together, our study supports that regulatory mechanisms at chromatin level may play an essential role in activating primary and secondary metabolic pathways to regulate VOC synthesis in petunia flowers.

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