scholarly journals HDAC1 SUMOylation promotes Argonaute directed transcriptional silencing in C. elegans

2020 ◽  
Author(s):  
Heesun Kim ◽  
Yue-He Ding ◽  
Gangming Zhang ◽  
Yong-Hong Yan ◽  
Darryl Conte ◽  
...  
Keyword(s):  
Chromatin Remodeling ◽  
De Novo ◽  
Transcriptional Silencing ◽  
Nurd Complex ◽  
Nucleosome Remodeling ◽  
C Elegans ◽  
Argonaute Proteins ◽  
Associated Proteins ◽  
Heterochromatin Silencing

SUMMARYEukaryotic cells use guided search to coordinately control dispersed genetic elements. The transitive effectors of these mechanisms, Argonaute proteins and their small-RNA co-factors, engage nascent RNAs and chromatin-associated proteins to direct transcriptional silencing. The small ubiquitin-like modifier (SUMO) has been shown to promote the induction and maintenance of silent chromatin (called heterochromatin) in yeast, plants, and animals. Here we show that Argonaute-directed transcriptional silencing in C. elegans requires SUMOylation of the type 1 histone deacetylase HDA-1. SUMOylation of HDA-1 promotes interactions with components of the nucleosome remodeling and deacetylase (NuRD) complex and with the nuclear Argonaute HRDE-1/WAGO-9. Our findings suggest how HDAC1 SUMOylation promotes the association of HDAC and other chromatin remodeling factors with a nuclear Argonaute in order to initiate de novo heterochromatin silencing.

scholarly journals HDAC1 SUMOylation promotes Argonaute-directed transcriptional silencing in C. elegans

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Heesun Kim ◽  
Yue-He Ding ◽  
Gangming Zhang ◽  
Yong-Hong Yan ◽  
Darryl Conte ◽  
...  
Keyword(s):  
Chromatin Remodeling ◽  
De Novo ◽  
Transcriptional Silencing ◽  
Silent Chromatin ◽  
Guided Search ◽  
C Elegans ◽  
Argonaute Proteins ◽  
Associated Proteins ◽  
Heterochromatin Silencing

Eukaryotic cells use guided search to coordinately control dispersed genetic elements. Argonaute proteins and their small RNA cofactors engage nascent RNAs and chromatin-associated proteins to direct transcriptional silencing. The small ubiquitin-like modifier (SUMO) has been shown to promote the formation and maintenance of silent chromatin (called heterochromatin) in yeast, plants, and animals. Here, we show that Argonaute-directed transcriptional silencing in Caenorhabditis elegans requires SUMOylation of the type 1 histone deacetylase HDA-1. Our findings suggest how SUMOylation promotes the association of HDAC1 with chromatin remodeling factors and with a nuclear Argonaute to initiate de novo heterochromatin silencing.

scholarly journals Functionally non-redundant paralogs spe-47 and spe-50 encode FB-MO associated proteins and interact with him-8

2020 ◽  
Author(s):  
Jessica N. Clark ◽  
Gaurav Prajapati ◽  
Fermina Aldaco ◽  
Thomas J. Sokolich ◽  
Steven Keung ◽  
...  
Keyword(s):  
Phylogenetic Analysis ◽  
Chromatin Remodeling ◽  
Duplication Event ◽  
Sperm Function ◽  
C Elegans ◽  
Conserved Sequence ◽  
Long Period ◽  
Normal Sperm ◽  
Number Of Genes ◽  
Associated Proteins

AbstractThe activation of C. elegans spermatids to crawling spermatozoa is affected by a number of genes including spe-47. Here, we investigate a paralog to spe-47: spe-50, which has a highly conserved sequence and expression, but which is not functionally redundant to spe-47. Phylogenetic analysis indicates that the duplication event that produced the paralogs occurred prior to the radiation of the Caenorhabditis species included in the analysis, allowing a long period for the paralogs to diverge in function. Furthermore, we observed that knockout mutations in both genes, either alone or together, have little effect on sperm function. However, hermaphrodites harboring both knockout mutations combined with a third mutation in the him-8 gene are nearly self-sterile due to a sperm defect, even though they have numerous apparently normal sperm within their spermathecae. We suggest that the sperm in these triple mutants are defective in fusing with oocytes, and that the effect of the him-8 mutation is due to its role in chromatin remodeling.

scholarly journals CHD4-NURD controls spermatogonia survival and differentiation

2019 ◽  
Author(s):  
Rodrigo O. de Castro ◽  
Victor Goitea ◽  
Luciana Previato ◽  
Agustin Carbajal ◽  
Courtney T. Griffin ◽  
...  
Keyword(s):  
Germ Cell ◽  
Cell Survival ◽  
Chromatin Remodeling ◽  
Male Gamete ◽  
Stem Cell Population ◽  
Nurd Complex ◽  
Nucleosome Remodeling ◽  
Testis Development ◽  
Expression Of Genes ◽  
Chromatin Remodeling Complexes

AbstractTestis development and sustained germ cell production in adults rely on the establishment of spermatogonia stem cells and their proper differentiation into mature gametes. Control of these processes involves not only promoting the expression of genes required for cell survival and differentiation but also repressing other cell fates. This level of transcriptional control requires chromatin-remodeling complexes that restrict or promote transcription machinery. Here, we investigated the roles of the NUcleosome Remodeling and Deacetylase (NURD) complex during spermatogenesis. Our cellular and biochemical analyses revealed differential expression and composition of NURD subunits in gametocytes at different stages of testis development. Germ cell-specific deletion of the NURD catalytic component CHD4, but not CHD3, resulted in arrested early gamete development due to failed cell survival of the undifferentiated spermatogonia stem cell population. Genome-wide CHD4 chromatin localization and transcriptomic analyses revealed that CHD4 binds the promoters and regulates the expression of genes involved in spermatogonia cell survival and differentiation. These results uncover the requirements of CHD4 in mammalian gonad development, and point to unique roles for the NURD complex with respect to other chromatin remodelers during gamete development.Significance StatementGametogenesis is a fundamental developmental program required for sustained fertility and survival of all sexually reproducing species. The developing male gamete undergoes numerous cell divisions and developmental stage transitions that are carefully monitored by epigenetic mechanisms. One prominent mechanism is directed by chromatin remodeling complexes, which modify chromatin structure and thereby control fundamental cellular processes such as gene transcription. In this work, we focused in understanding the role of CHD4 and CHD3 proteins, catalytic subunits of the NURD chromatin-remodeling complex, in mouse gametogenesis. We find that CHD4 has an essential function in gametogenesis, with an absolute requirement for survival of spermatogonia populations in the developing testis. This is accompanied by CHD4-mediated transcriptional regulation of genes important for spermatogonia survival, and differentiation.

Chromatin remodeling complexes: ATP-dependent machines in action

2005 ◽  
Vol 83 (4) ◽  
pp. 405-417 ◽  
Author(s):  
Cotteka N Johnson ◽  
Nicholas L Adkins ◽  
Philippe Georgel
Keyword(s):  
Chromatin Remodeling ◽  
Atp Hydrolysis ◽  
Nucleosome Remodeling ◽  
Core Histones ◽  
Associated Proteins ◽  
Chromatin Template ◽  
Chromatin Remodeling Complexes ◽  
The Individual ◽  
Insight Into

Since the initial characterization of chromatin remodeling as an ATP-dependent process, many studies have given us insight into how nucleosome-remodeling complexes can affect various nuclear functions. However, the multistep DNA-histone remodeling process has not been completely elucidated. Although new studies are published on a nearly weekly basis, the nature and roles of interactions of the individual SWI/SNF- and ISWI-based remodeling complexes and DNA, core histones, and other chromatin-associated proteins are not fully understood. In addition, the potential changes associated with ATP recruitment and its subsequent hydrolysis have not been fully characterized. This review explores possible mechanisms by which chromatin-remodeling complexes are recruited to specific loci, use ATP hydrolysis to achieve actual remodeling through disruption of DNA-histone interactions, and are released from their chromatin template. We propose possible roles for ATP hydrolysis in a chromatin-release/target-scanning process that offer an alternative to or complement the often overlooked function of delivering the energy required for sliding or dislodging specific subsets of core histones.Key words: chromatin remodeling, SWI/SNF, ISWI, APT hydrolysis.

scholarly journals Unique Protein Interaction Networks Define The Chromatin Remodeling Module of The NuRD Complex

2021 ◽  
Author(s):  
Mehdi Sharifi Tabar ◽  
Caroline Giardina ◽  
Yue Julie Feng ◽  
Habib Francis ◽  
Hakimeh Moghaddas Sani ◽  
...  
Keyword(s):  
Chromatin Remodeling ◽  
Protein Interaction ◽  
Treatment Strategies ◽  
Interaction Network ◽  
Terminal Segment ◽  
Mass Spectrometry Analysis ◽  
Nurd Complex ◽  
Nucleosome Remodeling ◽  
Spectrometry Analysis ◽  
Underlying Mechanisms

AbstractThe combination of four proteins and their paralogues including MBD2/3, GATAD2A/B, CDK2AP1, and CHD3/4/5, which we refer to as the MGCC module, form the chromatin remodeling module of the Nucleosome Remodeling and Deacetylase (NuRD) complex, a gene repressor complex. Specific paralogues of the MGCC subunits such as MBD2 and CHD4 are amongst the key repressors of adult-stage fetal globin and provide important targets for molecular therapies in beta (β)-thalassemia. However, mechanisms by which the MGCC module acquires paralogue-specific function and specificity have not been addressed to date. Understanding the protein-protein interaction (PPI) network of the MGCC subunits is essential in defining underlying mechanisms and developing treatment strategies. Therefore, using pulldown followed by mass spectrometry analysis (PD-MS) we report a proteome-wide interaction network of the MGCC module in a paralogue-specific manner. Our data also demonstrate that the disordered C-terminal region of CHD3/4/5 is a gateway to incorporate remodeling activity into both the ChAHP (CHD4, ADNP, HP1γ) and NuRD complexes in a mutually exclusive manner. We define a short aggregation prone region (APR) within the C-terminal segment of GATAD2B that is essential for the interaction of CHD4 and CDK2AP1 with the NuRD complex. Finally, we also report an association of CDK2AP1 with the Nuclear Receptor Co-Repressor (NCOR) complex. Overall, this study provides insight into the possible mechanisms through which the MGCC module can achieve specificity and diverse biological functions.

scholarly journals Evolution of Yin and Yang isoforms of a chromatin remodeling subunit precedes the creation of two genes

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Wen Xu ◽  
Lijiang Long ◽  
Yuehui Zhao ◽  
Lewis Stevens ◽  
Irene Felipe ◽  
...  
Keyword(s):  
Chromatin Remodeling ◽  
De Novo ◽  
Phenotypic Diversity ◽  
Laboratory Strain ◽  
Duplication Event ◽  
C Elegans ◽  
Genetic Position ◽  
Yin And Yang ◽  
The Creation ◽  
Gene Sharing

Genes can encode multiple isoforms, broadening their functions and providing a molecular substrate to evolve phenotypic diversity. Evolution of isoform function is a potential route to adapt to new environments. Here we show that de novo, beneficial alleles in the nurf-1 gene became fixed in two laboratory lineages of C. elegans after isolation from the wild in 1951, before methods of cryopreservation were developed. nurf-1 encodes an ortholog of BPTF, a large (>300 kD) multidomain subunit of the NURF chromatin remodeling complex. Using CRISPR-Cas9 genome editing and transgenic rescue, we demonstrate that in C. elegans, nurf-1 has split into two, largely non-overlapping isoforms (NURF-1.D and NURF-1.B, which we call Yin and Yang, respectively) that share only two of 26 exons. Both isoforms are essential for normal gametogenesis but have opposite effects on male/female gamete differentiation. Reproduction in hermaphrodites, which involves production of both sperm and oocytes, requires a balance of these opposing Yin and Yang isoforms. Transgenic rescue and genetic position of the fixed mutations suggest that different isoforms are modified in each laboratory strain. In a related clade of Caenorhabditis nematodes, the shared exons have duplicated, resulting in the split of the Yin and Yang isoforms into separate genes, each containing approximately 200 amino acids of duplicated sequence that has undergone accelerated protein evolution following the duplication. Associated with this duplication event is the loss of two additional nurf-1 transcripts, including the long-form transcript and a newly identified, highly expressed transcript encoded by the duplicated exons. We propose these lost transcripts are non-functional side products necessary to transcribe the Yin and Yang transcripts in the same cells. Our work demonstrates how gene sharing, through the production of multiple isoforms, can precede the creation of new, independent genes.

scholarly journals Evolution of Yin and Yang isoforms of a chromatin remodeling subunit results in the creation of two genes

2019 ◽  
Author(s):  
Wen Xu ◽  
Lijiang Long ◽  
Yuehui Zhao ◽  
Lewis Stevens ◽  
Ronald E. Ellis ◽  
...  
Keyword(s):  
Chromatin Remodeling ◽  
De Novo ◽  
Phenotypic Diversity ◽  
Laboratory Strain ◽  
Duplication Event ◽  
C Elegans ◽  
Genetic Position ◽  
Long Form ◽  
Yin And Yang ◽  
The Creation

AbstractGenes can encode multiple isoforms, broadening their functions and providing a molecular substrate to evolve phenotypic diversity. Evolution of isoform function is a potential route to adapt to new environments. Here we show that de novo, beneficial alleles in the nurf-1 gene fixed in two laboratory strains of C. elegans after isolation from the wild in 1951, before methods of cryopreservation were developed. nurf-1 encodes an ortholog of BPTF, a large (>300kD) multidomain subunit of the NURF chromatin remodeling complex. Using CRISPR-Cas9 genome editing and transgenic rescue, we demonstrate that in C. elegans, nurf-1 has split into two, largely non-overlapping isoforms (NURF-1.B and NURF-1.D, which we call Yin and Yang) that share only two of 26 exons. Both isoforms are essential for normal gametogenesis but have opposite effects on male/female gamete differentiation. Reproduction in hermaphrodites, which involves production of both sperm and oocytes, requires a balance of these opposing Yin and Yang isoforms. Transgenic rescue and genetic position of the fixed mutations suggest that different isoforms are modified in each laboratory strain. In a related clade of Caenorhabditis nematodes, the shared exons have duplicated, resulting in the split of the Yin and Yang isoforms into separate genes, each containing approximately 200 amino acids of duplicated sequence that has undergone accelerated protein evolution following the duplication. Associated with this duplication event is the loss of two additional nurf-1 transcripts, including the long-form transcript and a newly identified, highly expressed transcript encoded by the duplicated exons. We propose these lost transcripts are non-functional biproducts necessary to transcribe the Yin and Yang transcripts in the same cells. Our work suggests that evolution of nurf-1 isoforms in nematodes creates adaptive conflict that can be resolved by the creation of new, independent genes.

scholarly journals The conserved histone chaperone LIN-53 links lifespan and healthspan regulation in Caenorhabditis elegans

2019 ◽  
Author(s):  
Stefanie Müthel ◽  
Bora Uyar ◽  
Mei He ◽  
Anne Krause ◽  
Burcu Vitrinel ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Memory Loss ◽  
Histone Chaperone ◽  
Premature Aging ◽  
Biological Processes ◽  
Nurd Complex ◽  
Metabolome Analysis ◽  
Nucleosome Remodeling ◽  
C Elegans ◽  
Evolutionarily Conserved

SummaryWhether extension of lifespan provides an extended time without health deteriorations is an important issue for human aging. However, to which degree lifespan and healthspan regulation might be linked is not well understood. Chromatin factors could be involved in linking both aging aspects, as epigenetic mechanisms bridge regulation of different biological processes. The epigenetic factor LIN-53 (RBBP4/7) is required for safeguarding cell identities in Caenorhabditis elegans as well as mammals and for preventing memory loss and premature aging in humans. LIN-53 is a histone chaperone that associates with different chromatin-regulating complexes. We show that LIN-53 interacts with the Nucleosome remodeling and deacteylase (NuRD)-complex in C. elegans muscles to promote healthy locomotion during aging. While mutants for other NuRD members show a normal lifespan, animals lacking LIN-53 die early because LIN-53 depletion affects also the Histone deacetylase complex Sin3, which is required for a normal lifespan. To determine why lin-53 and sin-3 mutants die early, we performed transcriptome and metabolome analysis and found that levels of the disaccharide Trehalose are significantly decreased in both mutants. As Trehalose is required for normal lifespan in C. elegans, lin-53 and sin-3 mutants could be rescued by either feeding with Trehalose or increasing Trehalose levels via the Insulin/IGF1 signaling pathway. Overall, our findings suggest that LIN-53 is required for maintaining lifespan and promoting healthspan through discrete chromatin regulatory mechanisms. Since both LIN-53 and its mammalian homologs safeguard cell identities, it is conceivable that its implication in lifespan and healthspan regulation is also evolutionarily conserved.

scholarly journals GFI1 tethers the NuRD complex to open and transcriptionally active chromatin in myeloid progenitors

2021 ◽  
Author(s):  
Anne Helness ◽  
Jennifer Fraszczak ◽  
Charles Joly-Beauparlant ◽  
Halil Bagci ◽  
Christian Trahan ◽  
...  
Keyword(s):  
Chromatin Remodeling ◽  
Target Genes ◽  
Myeloid Differentiation ◽  
Open Chromatin ◽  
Nurd Complex ◽  
Active Chromatin ◽  
Nucleosome Remodeling ◽  
Nucleosome Organization ◽  
Active Transcription ◽  
Neutrophil Differentiation

Abstract GFI1 is a SNAG-domain, DNA binding transcriptional repressor which controls myeloid differentiation, in particular the formation of neutrophils. Here we show that GFI1 interacts with the chromodomain helicase CHD4 and other components of the “Nucleosome remodeling and deacetylase” (NuRD) complex. In granulo-monocytic precursors, GFI1, CHD4 or GFI1/CHD4 complexes occupy sites of open chromatin enriched for histone marks associated with active transcription suggesting that GFI1 recruits the NuRD complex to target genes that are regulated by active or bivalent promoters and active enhancers. Our data also show that GFI1 and GFI1/CHD4 complexes occupy promoters of different sets of genes that are either enriched for IRF1 or SPI-1 consensus sites, respectively. During neutrophil differentiation, overall chromatin closure and depletion of H3K4me2 occurs at different degrees depending on whether GFI1, CHD4 or both are present, indicating that GFI1 affects the chromatin remodeling activity of the NuRD complex. Moreover, GFI1/CHD4 complexes regulate chromatin openness and histone modifications differentially to enable regulation of target genes affecting the signaling pathways of the immune response or nucleosome organization or cellular metabolic processes.

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