A Role for Nuclear Actin in HDAC 1 and 2 Regulation

Serebryannyy, Leonid A.; Cruz, Christina; Lanerolle, Primal de

doi:10.1038/srep28460

Cited by 57 publications

(50 citation statements)

References 52 publications

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“…Similarly, depleting nuclear actin through changes in growth factors or extracellular molecules has been reported to inhibit RNAPII activity, and this inhibition can be rescued by expressing NLS-R62D-β-actin (Spencer et al, 2011). These data, which support the notion that monomeric actin is important in maintaining transcription, are consistent with the previous demonstration that monomeric nuclear actin interacts with chromatin remodeling complexes (Kapoor and Shen, 2014;Serebryannyy et al, 2016) and the transcription factor MAL (Vartiainen et al, 2007).…”

Section: Discussionsupporting

confidence: 88%

Persistent nuclear actin filaments inhibit transcription by RNA polymerase II

Serebryannyy

Parilla

Annibale

et al. 2016

Journal of Cell Science

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Actin is abundant in the nucleus and it is clear that nuclear actin has important functions. However, mystery surrounds the absence of classical actin filaments in the nucleus. To address this question, we investigated how polymerizing nuclear actin into persistent nuclear actin filaments affected transcription by RNA polymerase II. Nuclear filaments impaired nuclear actin dynamics by polymerizing and sequestering nuclear actin. Polymerizing actin into stable nuclear filaments disrupted the interaction of actin with RNA polymerase II and correlated with impaired RNA polymerase II localization, dynamics, gene recruitment, and reduced global transcription and cell proliferation. Polymerizing and crosslinking nuclear actin in vitro similarly disrupted the actin-RNA-polymerase-II interaction and inhibited transcription. These data rationalize the general absence of stable actin filaments in mammalian somatic nuclei. They also suggest a dynamic pool of nuclear actin is required for the proper localization and activity of RNA polymerase II.

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Section: Discussionsupporting

confidence: 88%

Persistent nuclear actin filaments inhibit transcription by RNA polymerase II

Serebryannyy

Parilla

Annibale

et al. 2016

Journal of Cell Science

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“…A recent study in epidermal stem cells also demonstrated that a reduced level of nuclear actin in response to mechanical stretch can lead to chromatin rearrangement and associated changes in H3K9Me3 and H3K27Me3 levels (44). In contrast, general chromatin decompaction may be a consequence of altered histone deacetylase (HDAC) activity in the absence of b-actin, given that nuclear actin has recently been described to interact with HDACs and to regulate their enzymatic activity (45).…”

Section: Discussionmentioning

confidence: 99%

β‐Actin‐dependent global chromatin organization and gene expression programs control cellular identity

et al. 2018

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During differentiation and development, cell fate and identity are established by waves of genetic reprogramming. Although the mechanisms are largely unknown, during these events, dynamic chromatin reorganization is likely to ensure that multiple genes involved in the same cellular functions are coregulated, depending on the nuclear environment. In this study, using high-content screening of embryonic fibroblasts from a β-actin knockout (KO) mouse, we found major chromatin rearrangements and changes in histone modifications, such as methylated histone (H)3-lysine-(K)9. Genome-wide H3K9 trimethylation-(Me)3 landscape changes correlate with gene up- and down-regulation in β-actin KO cells. Mechanistically, we found loss of chromatin association by the Brahma-related gene ( Brg)/Brahma-associated factor (BAF) chromatin remodeling complex subunit Brg1 in the absence of β-actin. This actin-dependent chromatin reorganization was concomitant with the up-regulation of sets of genes involved in angiogenesis, cytoskeletal organization, and myofibroblast features in β-actin KO cells. Some of these genes and phenotypes were gained in a β-actin dose-dependent manner. Moreover, reintroducing a nuclear localization signal-containing β-actin in the knockout cells affected nuclear features and gene expression. Our results suggest that, by affecting the genome-wide organization of heterochromatin through the chromatin-binding activity of the BAF complex, β-actin plays an essential role in the determination of gene expression programs and cellular identity.-Xie, X., Almuzzaini, B., Drou, N., Kremb, S., Yousif, A., Östlund Farrants, A.-K., Gunsalus, K., Percipalle, P. β-Actin-dependent global chromatin organization and gene expression programs control cellular identity.

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“…More recently, actin was identified as a functional binding partner of histone deacteylase (HDAC) 1 and 2 of the nucleosome remodeling histone deacetylase (NuRD) complex and the corepressor for element-1-silencing transcription factor (CoREST) complex (Serebryannyy et al, 2016a). Nuclear actin monomers bind HDACs and inhibit their function, whereas stimulation of nuclear actin polymerization alleviates this suppression (Serebryannyy et al, 2016a). HDACs remove acetyl-moieties from histones, relaxing chromatin and promoting transcription (Seto and Yoshida, 2014).…”

Section: Chromatin Organizationmentioning

confidence: 99%

Nuclear Actin: From Discovery to Function

Kelpsch

Tootle

2018

The Anatomical Record

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While actin was discovered in the nucleus over 50 years ago, research lagged for decades due to strong skepticism. The revitalization of research into nuclear actin occurred after it was found that cellular stresses induce the nuclear localization and alter the structure of actin. These studies provided the first hints that actin has a nuclear function. Subsequently, it was established that the nuclear import and export of actin is highly regulated. While the structures of nuclear actin remain unclear, it can function as monomers, polymers, and even rods. Furthermore, even within a given structure, distinct pools of nuclear actin that can be differentially labeled have been identified. Numerous mechanistic studies have uncovered an array of functions for nuclear actin. It regulates the activity of RNA polymerases, as well as specific transcription factors. Actin also modulates the activity of several chromatin remodeling complexes and histone deacetylases, to ultimately impinge on transcriptional programing and DNA damage repair. Further, nuclear actin mediates chromatin movement and organization. It has roles in meiosis and mitosis, and these functions may be functionally conserved from ancient bacterial actin homologs. The structure and integrity of the nuclear envelope and sub-nuclear compartments are also regulated by nuclear actin. Furthermore, nuclear actin contributes to human diseases like cancer, neurodegeneration, and myopathies. Here, we explore the early discovery of actin in the nucleus and discuss the forms and functions of nuclear actin in both normal and disease contexts

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A Role for Nuclear Actin in HDAC 1 and 2 Regulation

Cited by 57 publications

References 52 publications

Persistent nuclear actin filaments inhibit transcription by RNA polymerase II

Persistent nuclear actin filaments inhibit transcription by RNA polymerase II

β‐Actin‐dependent global chromatin organization and gene expression programs control cellular identity

Nuclear Actin: From Discovery to Function

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