scholarly journals Chromatin Remodeling in the Brain-a NuRDevelopmental Odyssey

2021 ◽  
Vol 22 (9) ◽  
pp. 4768
Author(s):  
Sarah Larrigan ◽  
Sujay Shah ◽  
Alex Fernandes ◽  
Pierre Mattar
Keyword(s):  
Brain Development ◽  
Chromatin Remodeling ◽  
Neural Progenitors ◽  
Nurd Complex ◽  
Glial Differentiation ◽  
Nucleosome Remodeling ◽  
Chromatin Remodeling Complexes ◽  
Genetic Level ◽  
The Brain

During brain development, the genome must be repeatedly reconfigured in order to facilitate neuronal and glial differentiation. A host of chromatin remodeling complexes facilitates this process. At the genetic level, the non-redundancy of these complexes suggests that neurodevelopment may require a lexicon of remodelers with different specificities and activities. Here, we focus on the nucleosome remodeling and deacetylase (NuRD) complex. We review NuRD biochemistry, genetics, and functions in neural progenitors and neurons.

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.

scholarly journals Generation of Vascularized Brain Organoids to Study Neurovascular Interactions

2022 ◽  
Author(s):  
Zhen-Ge Luo ◽  
Xin-Yao Sun ◽  
Xiang-Chun Ju ◽  
Yang Li ◽  
Peng-Ming Zeng ◽  
...  
Keyword(s):  
Brain Development ◽  
Neural Development ◽  
Immune Cells ◽  
Aging Process ◽  
Neural Progenitors ◽  
Brain Disorders ◽  
Specific Population ◽  
Neurovascular Interactions ◽  
The Brain

The recently developed brain organoids have been used to recapitulate the processes of brain development and related diseases. However, the lack of vasculatures, which regulate neurogenesis, brain disorders, and aging process, limits the utility of brain organoids. In this study, we induced vessel and brain organoids respectively, and then fused two types of organoids together to obtain vascularized brain organoids. The fused brain organoids were engrafted with robust vascular network-like structures, and exhibited increased number of neural progenitors, in line with the possibility that vessels regulate neural development. Fusion organoids also contained functional blood-brain-barrier (BBB)-like structures, as well as microglial cells, a specific population of immune cells in the brain. The incorporated microglia responded actively to immune stimuli to the fused brain organoids. Thus, the fusion organoids established in this study allow modeling interactions between the neuronal and non-neuronal components in vitro, in particular the vasculature and microglia niche.

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 A Casz1–NuRD complex regulates temporal identity transitions in neural progenitors

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Pierre Mattar ◽  
Christine Jolicoeur ◽  
Thanh Dang ◽  
Sujay Shah ◽  
Brian S. Clark ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Neural Progenitor Cells ◽  
Neural Progenitors ◽  
Biochemical Process ◽  
Nurd Complex ◽  
Nucleosome Remodeling ◽  
Correct Sequence ◽  
Different Types ◽  
Temporal Identity ◽  
Identity Transitions

AbstractNeural progenitor cells undergo identity transitions during development to ensure the generation different types of neurons and glia in the correct sequence and proportions. A number of temporal identity factors that control these transitions in progenitor competence have been identified, but the molecular mechanisms underlying their function remain unclear. Here, we asked how Casz1, the mammalian orthologue of Drosophila castor, regulates competence during retinal development. We show that Casz1 is required to control the transition between neurogenesis and gliogenesis. Using BioID proteomics, we reveal that Casz1 interacts with the nucleosome remodeling and deacetylase (NuRD) complex in retinal cells. Finally, we show that both the NuRD and the polycomb repressor complexes are required for Casz1 to promote the rod fate and suppress gliogenesis. As additional temporal identity factors have been found to interact with the NuRD complex in other contexts, we propose that these factors might act through this common biochemical process to regulate neurogenesis.

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 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 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.

scholarly journals The Roles of Hippo Signaling Transducers Yap and Taz in Chromatin Remodeling

Cells ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 502 ◽  
Author(s):  
Ryan E. Hillmer ◽  
Brian A. Link
Keyword(s):  
Chromatin Remodeling ◽  
Transcriptional Control ◽  
Target Genes ◽  
Hippo Signaling ◽  
Major Pathway ◽  
Nucleosome Remodeling ◽  
Cellular Processes ◽  
Disease States ◽  
Chromatin Remodeling Complexes ◽  
Dna Packing

Hippo signaling controls cellular processes that ultimately impact organogenesis and homeostasis. Consequently, disease states including cancer can emerge when signaling is deregulated. The major pathway transducers Yap and Taz require cofactors to impart transcriptional control over target genes. Research into Yap/Taz-mediated epigenetic modifications has revealed their association with chromatin-remodeling complex proteins as a means of altering chromatin structure, therefore affecting accessibility and activity of target genes. Specifically, Yap/Taz have been found to associate with factors of the GAGA, Ncoa6, Mediator, Switch/sucrose nonfermentable (SWI/SNF), and Nucleosome Remodeling and Deacetylase (NuRD) chromatin-remodeling complexes to alter the accessibility of target genes. This review highlights the different mechanisms by which Yap/Taz collaborate with other factors to modify DNA packing at specific loci to either activate or repress target gene transcription.

scholarly journals Chromatin Remodeling Proteins Interact with Pericentrin to Regulate Centrosome Integrity

2007 ◽  
Vol 18 (9) ◽  
pp. 3667-3680 ◽  
Author(s):  
James Edward Sillibourne ◽  
Bénédicte Delaval ◽  
Sambra Redick ◽  
Manisha Sinha ◽  
Stephen John Doxsey
Keyword(s):  
Rna Interference ◽  
Chromatin Remodeling ◽  
Chromosome Segregation ◽  
Time Lapse ◽  
Dna Binding Protein ◽  
Nurd Complex ◽  
Yeast Two Hybrid ◽  
Nucleosome Remodeling ◽  
Time Lapse Imaging ◽  
Two Hybrid

Pericentrin is an integral centrosomal component that anchors regulatory and structural molecules to centrosomes. In a yeast two-hybrid screen with pericentrin we identified chromodomain helicase DNA-binding protein 4 (CHD4/Mi2β). CHD4 is part of the multiprotein nucleosome remodeling deacetylase (NuRD) complex. We show that many NuRD components interacted with pericentrin by coimmunoprecipitation and that they localized to centrosomes and midbodies. Overexpression of the pericentrin-binding domain of CHD4 or another family member (CHD3) dissociated pericentrin from centrosomes. Depletion of CHD3, but not CHD4, by RNA interference dissociated pericentrin and γ-tubulin from centrosomes. Microtubule nucleation/organization, cell morphology, and nuclear centration were disrupted in CHD3-depleted cells. Spindles were disorganized, the majority showing a prometaphase-like configuration. Time-lapse imaging revealed mitotic failure before chromosome segregation and cytokinesis failure. We conclude that pericentrin forms complexes with CHD3 and CHD4, but a distinct CHD3–pericentrin complex is required for centrosomal anchoring of pericentrin/γ-tubulin and for centrosome integrity.

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