scholarly journals Biophysics of Chromatin Remodeling

2021 ◽  
Vol 50 (1) ◽  
Author(s):  
Ilana M. Nodelman ◽  
Gregory D. Bowman

As primary carriers of epigenetic information and gatekeepers of genomic DNA, nucleosomes are essential for proper growth and development of all eukaryotic cells. Although they are intrinsically dynamic, nucleosomes are actively reorganized by ATP-dependent chromatin remodelers. Chromatin remodelers contain helicase-like ATPase motor domains that can translocate along DNA, and a long-standing question in the field is how this activity is used to reposition or slide nucleosomes. In addition to ratcheting along DNA like their helicase ancestors, remodeler ATPases appear to dictate specific alternating geometries of the DNA duplex, providing an unexpected means for moving DNA past the histone core. Emerging evidence supports twist-based mechanisms for ATP-driven repositioning of nucleosomes along DNA. In this review, we discuss core experimental findings and ideas that have shaped the view of how nucleosome sliding may be achieved. Expected final online publication date for the Annual Review of Biophysics, Volume 50 is May 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Author(s):  
Paul B. Talbert ◽  
Steven Henikoff

Nucleosomes wrap DNA and impede access for the machinery of transcription. The core histones that constitute nucleosomes are subject to a diversity of posttranslational modifications, or marks, that impact the transcription of genes. Their functions have sometimes been difficult to infer because the enzymes that write and read them are complex, multifunctional proteins. Here, we examine the evidence for the functions of marks and argue that the major marks perform a fairly small number of roles in either promoting transcription or preventing it. Acetylations and phosphorylations on the histone core disrupt histone-DNA contacts and/or destabilize nucleosomes to promote transcription. Ubiquitylations stimulate methylations that provide a scaffold for either the formation of silencing complexes or resistance to those complexes, and carry a memory of the transcriptional state. Tail phosphorylations deconstruct silencing complexes in particular contexts. We speculate that these fairly simple roles form the basis of transcriptional regulation by histone marks. Expected final online publication date for the Annual Review of Genomics and Human Genetics Volume 22 is August 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.


Author(s):  
Samaneh Ghassabi Kondalaji ◽  
Gregory D. Bowman

In transcriptionally active genes, nucleosome positions in promoters are regulated by nucleosome displacing factors (NDFs) and chromatin remodeling enzymes. Depletion of NDFs or the RSC chromatin remodeler shrinks or abolishes the nucleosome depleted regions (NDRs) in promoters, which can suppress gene activation and result in cryptic transcription. Despite their vital cellular functions, how the action of chromatin remodelers may be directly affected by site-specific binding factors like NDFs is poorly understood. Here we demonstrate that two NDFs, Reb1 and Cbf1, can direct both Chd1 and RSC chromatin remodeling enzymes in vitro , stimulating repositioning of the histone core away from their binding sites. Interestingly, although the Pho4 transcription factor had a much weaker effect on nucleosome positioning, both NDFs and Pho4 were able to similarly redirect positioning of hexasomes. In chaperone-mediated nucleosome assembly assays, Reb1 but not Pho4 showed an ability to block deposition of the histone H3/H4 tetramer, but Reb1 did not block addition of the H2A/H2B dimer to hexasomes. Our in vitro results show that NDFs bias the action of remodelers to increase the length of the free DNA in the vicinity of their binding sites. These results suggest that NDFs could directly affect NDR architecture through chromatin remodelers.


eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
R Stefan Isaac ◽  
Fuguo Jiang ◽  
Jennifer A Doudna ◽  
Wendell A Lim ◽  
Geeta J Narlikar ◽  
...  

The CRISPR-Cas9 bacterial surveillance system has become a versatile tool for genome editing and gene regulation in eukaryotic cells, yet how CRISPR-Cas9 contends with the barriers presented by eukaryotic chromatin is poorly understood. Here we investigate how the smallest unit of chromatin, a nucleosome, constrains the activity of the CRISPR-Cas9 system. We find that nucleosomes assembled on native DNA sequences are permissive to Cas9 action. However, the accessibility of nucleosomal DNA to Cas9 is variable over several orders of magnitude depending on dynamic properties of the DNA sequence and the distance of the PAM site from the nucleosome dyad. We further find that chromatin remodeling enzymes stimulate Cas9 activity on nucleosomal templates. Our findings imply that the spontaneous breathing of nucleosomal DNA together with the action of chromatin remodelers allow Cas9 to effectively act on chromatin in vivo.


2021 ◽  
Vol 45 (1) ◽  
Author(s):  
Wenbo Tang ◽  
Shantanu P. Jadhav

When navigating through space, we must maintain a representation of our position in real time; when recalling a past episode, a memory can come back in a flash. Interestingly, the brain's spatial representation system, including the hippocampus, supports these two distinct timescale functions. How are neural representations of space used in the service of both real-world navigation and internal mnemonic processes? Recent progress has identified sequences of hippocampal place cells, evolving at multiple timescales in accordance with either navigational behaviors or internal oscillations, that underlie these functions. We review experimental findings on experience-dependent modulation of these sequential representations and consider how they link real-world navigation to time-compressed memories. We further discuss recent work suggesting the prevalence of these sequences beyond hippocampus and propose that these multiple-timescale mechanisms may represent a general algorithm for organizing cell assemblies, potentially unifying the dual roles of the spatial representation system in memory and navigation. Expected final online publication date for the Annual Review of Neuroscience, Volume 45 is July 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.


Author(s):  
Luke T. Izzo ◽  
Hayley C. Affronti ◽  
Kathryn E. Wellen

Metabolic and epigenetic reprogramming are characteristics of cancer cells that, in many cases, are linked. Oncogenic signaling, diet, and tumor microenvironment each influence the availability of metabolites that are substrates or inhibitors of epigenetic modifying enzymes. Reciprocally, altered expression or activity of epigenetic modifying enzymes can exert direct and indirect effects on cellular metabolism. In this article, we discuss the bidirectional relationship between epigenetics and metabolism in cancer. First, we focus on epigenetic control of metabolism, highlighting evidence that alterations in histone modifications, chromatin remodeling, or the enhancer landscape can drive metabolic features that support growth and proliferation. We then discuss metabolic regulation of chromatin-modifying enzymes and roles in tumor growth and progression. Throughout, we highlight proposed therapeutic and dietary interventions that leverage metabolic-epigenetic cross talk and have the potential to improve cancer therapy. Expected final online publication date for the Annual Review of Cancer Biology, Volume 5 is March 4, 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.


Author(s):  
Daphne Perlman ◽  
Marina Martínez-Álvaro ◽  
Sarah Moraïs ◽  
Ianina Altshuler ◽  
Live H. Hagen ◽  
...  

Animal microbiomes are occasionally considered as an extension of host anatomy, physiology, and even their genomic architecture. Their compositions encompass variable and constant portions when examined across multiple hosts. The latter, termed the core microbiome, is viewed as more accommodated to its host environment and suggested to benefit host fitness. Nevertheless, discrepancies in its definitions, characteristics, and importance to its hosts exist across studies. We survey studies that characterize the core microbiome, detail its current definitions and available methods to identify it, and emphasize the crucial need to upgrade and standardize the methodologies among studies. We highlight ruminants as a case study and discuss the link between the core microbiome and host physiology and genetics, as well as potential factors that shape it. We conclude with main directives of action to better understand the host–core microbiome axis and acquire the necessary insights into its controlled modulation. Expected final online publication date for the Annual Review of Animal Biosciences, Volume 10 is February 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.


Author(s):  
Elliott S. Chiu ◽  
Sue VandeWoude

Endogenous retroviruses (ERVs) serve as markers of ancient viral infections and provide invaluable insight into host and viral evolution. ERVs have been exapted to assist in performing basic biological functions, including placentation, immune modulation, and oncogenesis. A subset of ERVs share high nucleotide similarity to circulating horizontally transmitted exogenous retrovirus (XRV) progenitors. In these cases, ERV–XRV interactions have been documented and include ( a) recombination to result in ERV–XRV chimeras, ( b) ERV induction of immune self-tolerance to XRV antigens, ( c) ERV antigen interference with XRV receptor binding, and ( d) interactions resulting in both enhancement and restriction of XRV infections. Whereas the mechanisms governing recombination and immune self-tolerance have been partially determined, enhancement and restriction of XRV infection are virus specific and only partially understood. This review summarizes interactions between six unique ERV–XRV pairs, highlighting important ERV biological functions and potential evolutionary histories in vertebrate hosts. Expected final online publication date for the Annual Review of Animal Biosciences, Volume 9 is February 16, 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.


Author(s):  
Sarah Knuckey ◽  
Joshua D. Fisher ◽  
Amanda M. Klasing ◽  
Tess Russo ◽  
Margaret L. Satterthwaite

The human rights movement is increasingly using interdisciplinary, multidisciplinary, mixed-methods, and quantitative factfinding. There has been too little analysis of these shifts. This article examines some of the opportunities and challenges of these methods, focusing on the investigation of socioeconomic human rights. By potentially expanding the amount and types of evidence available, factfinding's accuracy and persuasiveness can be strengthened, bolstering rights claims. However, such methods can also present significant challenges and may pose risks in individual cases and to the human rights movement generally. Interdisciplinary methods can be costly in human, financial, and technical resources; are sometimes challenging to implement; may divert limited resources from other work; can reify inequalities; may produce “expertise” that disempowers rightsholders; and could raise investigation standards to an infeasible or counterproductive level. This article includes lessons learned and questions to guide researchers and human rights advocates considering mixed-methods human rights factfinding. Expected final online publication date for the Annual Review of Law and Social Science, Volume 17 is October 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.


2021 ◽  
Vol 50 (1) ◽  
Author(s):  
Simeon Floyd

Conversation analysis is a method for the systematic study of interaction in terms of a sequential turn-taking system. Research in conversation analysis has traditionally focused on speakers of English, and it is still unclear to what extent the system observed in that research applies to conversation more generally around the world. However, as this method is now being applied to conversation in a broader range of languages, it is increasingly possible to address questions about the nature of interactional diversity across different speech communities. The approach of pragmatic typology first applies sequential analysis to conversation from different speech communities and then compares interactional patterns in ways analogous to how traditional linguistic typology compares morphosyntax. This article discusses contemporary literature in pragmatic typology, including single-language studies and multilanguage comparisons reflecting both qualitative and quantitative methods. This research finds that microanalysis of face-to-face interaction can identify both universal trends and culture-specific interactional tendencies. Expected final online publication date for the Annual Review of Anthropology, Volume 50 is October 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.


Author(s):  
Yonit Maroudas-Sacks ◽  
Kinneret Keren

Morphogenesis is one of the most remarkable examples of biological pattern formation. Despite substantial progress in the field, we still do not understand the organizational principles responsible for the robust convergence of the morphogenesis process across scales to form viable organisms under variable conditions. Achieving large-scale coordination requires feedback between mechanical and biochemical processes, spanning all levels of organization and relating the emerging patterns with the mechanisms driving their formation. In this review, we highlight the role of mechanics in the patterning process, emphasizing the active and synergistic manner in which mechanical processes participate in developmental patterning rather than merely following a program set by biochemical signals. We discuss the value of applying a coarse-grained approach toward understanding this complex interplay, which considers the large-scale dynamics and feedback as well as complementing the reductionist approach focused on molecular detail. A central challenge in this approach is identifying relevant coarse-grained variables and developing effective theories that can serve as a basis for an integrated framework for understanding this remarkable pattern-formation process. Expected final online publication date for the Annual Review of Cell and Developmental Biology, Volume 37 is October 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.


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