Nuclear Myosin II Regulates the Assembly of Preinitiation Complex for ICAM-1 Gene Transcription

Li, Qingjie; Sarna, Sushil K.

doi:10.1053/j.gastro.2009.03.040

Cited by 55 publications

(76 citation statements)

References 44 publications

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“…MLCK activity has been shown to be necessary for TNFa-dependent NFkB activation and amplification of pro-survival signals (Wadgaonkar et al, 2003). Although a role for nuclear actin and myosin I motors during transcription has been established Philimonenko et al, 2004), it is unclear whether this model extends to other myosin motors (Li and Sarna, 2009).…”

Section: Discussionmentioning

confidence: 99%

“…Orange ovals, SC nuclei; blue circles, axons; red lines, inhibition; blue arrow, activation. describing the presence of its endogenous targets (myosin II and/ or MLC) in the nucleus of human and rodent cells (Li and Sarna, 2009;Ray et al, 2007). MLCK activity has been shown to be necessary for TNFa-dependent NFkB activation and amplification of pro-survival signals (Wadgaonkar et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

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MLCK regulates Schwann cell cytoskeletal organization, differentiation and myelination

Leitman¹,

Tewari²,

Horn³

et al. 2012

Development

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SummarySignaling through cyclic AMP (cAMP) has been implicated in the regulation of Schwann cell (SC) proliferation and differentiation. In quiescent SCs, elevation of cAMP promotes the expression of proteins associated with myelination such as Krox-20 and P0, and downregulation of markers associated with the non-myelinating SC phenotype. We have previously shown that the motor protein myosin II is required for the establishment of normal SC-axon interactions, differentiation and myelination, however, the mechanisms behind these effects are unknown. Here we report that the levels and activity of myosin light chain kinase (MLCK), an enzyme that regulates MLC phosphorylation in non-muscle cells, are dramatically downregulated in SCs after cAMP treatment, in a similar pattern to that of c-Jun, a known inhibitor of myelination. Knockdown of MLCK in SCs mimics the effect of cAMP elevation, inducing plasma membrane expansion and expression of Krox-20 and myelin proteins. Despite activation of myelin gene transcription these cells fail to make compact myelin when placed in contact with axons. Our data indicate that myosin II activity is differentially regulated at various stages during myelination and that in the absence of MLCK the processes of SC differentiation and compact myelin assembly are uncoupled.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

MLCK regulates Schwann cell cytoskeletal organization, differentiation and myelination

Leitman¹,

Tewari²,

Horn³

et al. 2012

Development

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“…We extracted cytoplasmic and nuclear extracts by using NE-PER nuclear and cytoplasmic extraction reagents (Thermo Scientific, Rockford, IL). We prepared whole cell lysates by using immunoprecipitation (IP) lysis buffer (22). Western blotting was performed as described previously (22).…”

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confidence: 99%

“…We used primary cultures of rat colonic circular smooth muscle cells (RCCSMC) in passage 2 or 3 for reporter assays. Transient transfection of Icam-1 reporter constructs, luciferase, and ␤-galactosidase (␤-Gal) assays were performed, as described previously (21,22).…”

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confidence: 99%

Nitric oxide modifies chromatin to suppress ICAM-1 expression during colonic inflammation

Sarna

2012

American Journal of Physiology-Gastrointestinal and Liver Physi

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Li Q, Sarna SK. Nitric oxide modifies chromatin to suppress ICAM-1 expression during colonic inflammation. Am J Physiol Gastrointest Liver Physiol 303: G103-G110, 2012. First published April 19, 2012 doi:10.1152/ajpgi.00381.2011 is an established inflammatory mediator. However, it remains controversial whether NO enhances the inflammatory response in the colon or suppresses it. We investigated the epigenetic regulation of Icam-1 expression by NO following induction of colonic inflammation in rats by 2,4,6-trinitrobenzene sulfonic (TNBS) acid and obtaining colonic muscularis externae tissues 24 h later. TNBS inflammation induced intercellular adhesion molecule-1 (ICAM-1) expression by translocating NF-B to the nucleus. The incubation of inflamed tissues with S-nitrosoglutathione (GSNO) did not affect the nuclear translocation of NF-B; however, it suppressed the NF-B binding to DNA. Chromatin immunoprecipitation analysis (ChIP)-qPCR assays showed that the increase in NF-B/DNA interaction following inflammation is due to the transcriptional downregulation of global HDAC3 and a decrease in its interaction with the DNA on the Icam-1 promoter containing the binding motifs of NF-B. The decrease in the association of histone deacetylase (HDAC) 3 with the Icam-1 promoter increased the acetylation of histone 4 lysine residue 12 (H4K12), which would favor chromatin relaxation and greater access of NF-B to its DNA binding sites. HDAC3 dissociation from the DNA did not affect the acetylation levels of H4K8 and H4K16. The NO release by GSNO countered the upregulation of Icam-1 by increasing the transcription of global HDAC3 and its association with the Icam-1 promoter, and by suppressing H4K12 acetylation. We conclude that chromatin modification by transcriptional downregulation of HDAC3 plays a critical role in the induction of the inflammatory response. NO may serve as an anti-inflammatory mediator during the acute stage of inflammation by blunting the downregulation of global HDAC3, increasing HDAC3 interaction with the nucleosomes containing the binding moieties of NF-B, reducing H4K12Ac to restrict the access of NF-B to DNA, and suppressing ICAM-1 expression. intercellular adhesion molecule-1; inflammation NITRIC OXIDE (NO) and inducible NO synthase (iNOS) are elevated in the inflamed tissues of patients with ulcerative colitis and Crohn's disease (9, 32, 37) as well as in the tissues of rodent models of these diseases, dextran sodium sulfate (DSS)-and trinitrobenzene sulfonic acid (TNBS)-induced inflammation, respectively (15). These findings suggest that NO may serve as an inflammatory mediator in inflammatory bowel disease. However, experiments in intact animal models have been inconclusive. Some studies found that prophylactic or therapeutic inhibition of iNOS attenuates gut inflammation and injury, implying that NO is deleterious (10,16,28). Other studies found that the blockade of iNOS by pharmacological inhibitors or knockout of the iNOS gene either has no effect or worsens the inflammatory response, suggesting t...

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“…However, most members of the myosin superfamily, including nuclear myosin I and most of the other myosins discovered in the nucleus, do not form filaments (Sellers, 2004). Although myosin II has been described in the nucleus (Rodgers, 2005;Li and Sarna, 2009), myosin II filaments are yet to be described in the nucleus. Nuclear myosin Va is found in nuclear speckles, which are (See poster insert) sites of RNA processing in transcriptionally active cells (Pranchevicius et al, 2008).…”

Section: Nuclear Myosinsmentioning

confidence: 99%

Nuclear actin and myosins at a glance

Lanerolle

2012

Journal of Cell Science

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Nuclear Myosin II Regulates the Assembly of Preinitiation Complex for ICAM-1 Gene Transcription

Cited by 55 publications

References 44 publications

MLCK regulates Schwann cell cytoskeletal organization, differentiation and myelination

MLCK regulates Schwann cell cytoskeletal organization, differentiation and myelination

Nitric oxide modifies chromatin to suppress ICAM-1 expression during colonic inflammation

Nuclear actin and myosins at a glance

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