Zic1 is a Transcriptional Repressor Through the Lamin A/C Promoter and has an Intrinsic Repressive Domain

Okumura, Koichi; Hosoe, Yuko; Nakajima, Noboru

doi:10.1248/jhs.50.423

Cited by 4 publications

(1 citation statement)

References 20 publications

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“…DNA methylation is an epigenetic mechanism by which gene activity can be regulated, but it was discounted as the foremost means of controlling LMNA levels -no consistent changes were observed in the methylation of the LMNA promoter either in a range of cell lines known to express different levels of A-type lamin protein (Swift et al, 2013b) or in tissues from patients with laminopathic disorders (Cortese et al, 2007). LMNA transcription has been reported to be controlled by transcription factors of the retinoic-acid receptor family (RAR and RXR family proteins; Okumura et al, 2004a;Okumura et al, 2004b;Olins et al, 2001;Shin et al, 2013;Swift et al, 2013b), with the resulting mRNA alternatively spliced to give the lamin-A and truncated lamin-C forms. Soft tissue generally preferentially expresses the lamin-C spliceoform (Swift et al, 2013b), and, in brain, the micro-RNA MIR-9 specifically targets and deactivates the mRNA of the lamin-A spliceoform (Jung et al, 2012;Jung et al, 2013).…”

Section: Mechanisms Of Lamin Regulationmentioning

confidence: 99%

The nuclear lamina is mechano-responsive to ECM elasticity in mature tissue

Swift

Discher

2014

Journal of Cell Science

182

166

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How cells respond to physical cues in order to meet and withstand the physical demands of their immediate surroundings has been of great interest for many years, with current research efforts focused on mechanisms that transduce signals into gene expression. Pathways that mechano-regulate the entry of transcription factors into the cell nucleus are emerging, and our most recent studies show that the mechanical properties of the nucleus itself are actively controlled in response to the elasticity of the extracellular matrix (ECM) in both mature and developing tissue. In this Commentary, we review the mechano-responsive properties of nuclei as determined by the intermediate filament lamin proteins that line the inside of the nuclear envelope and that also impact upon transcription factor entry and broader epigenetic mechanisms. We summarize the signaling pathways that regulate lamin levels and cell-fate decisions in response to a combination of ECM mechanics and molecular cues. We will also discuss recent work that highlights the importance of nuclear mechanics in niche anchorage and cell motility during development, hematopoietic differentiation and cancer metastasis, as well as emphasizing a role for nuclear mechanics in protecting chromatin from stress-induced damage.

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Section: Mechanisms Of Lamin Regulationmentioning

confidence: 99%

The nuclear lamina is mechano-responsive to ECM elasticity in mature tissue

Swift

Discher

2014

Journal of Cell Science

182

166

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The Nuclear Lamina: From Mechanosensing in Differentiation to Cancer Cell Migration

Irianto

Ivanovska

Swift

et al. 2016

Molecular and Cellular Mechanobiology

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Role of Zic Family Proteins in Transcriptional Regulation and Chromatin Remodeling

Hatayama

Aruga

2018

Advances in Experimental Medicine and Biology

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Proper functions of Zic proteins are essential for animals in health and disease. Here, we summarize our current understanding of the molecular properties and functions of the Zic family across animal species and paralog subtypes. Zics are basic proteins with some posttranslational modifications and can move to the cell nucleus via importin- and CRM1-based nucleocytoplasmic shuttling mechanisms. Degradation is mediated by the ubiquitin proteasome system. Many Zic proteins are capable of binding to two types of target DNA sequences (CTGCTG-core-type and GC-stretch-type). Recent chromatin immunoprecipitation assays showed that CTGCTG-core-type target sequences are enriched in enhancers. Nonetheless, the DNA binding is not always required for transcriptional regulation by Zic proteins. On the other hand, Zic proteins bind many proteins including transcription factors (Gli1-3, Tcf1 or Tcf4, Smad2 or Smad3, Oct4, Pax3, Cdx, and SRF), chromatin-remodeling factors (NuRD and NURF), and other nuclear enzymes (DNA-PK, PARP1, and RNA helicase A). Zic family-mediated gene expression control involves both their actions near the transcription start site and those affecting the global gene expression via binding to enhancers. Although Zic proteins perform essential functions in transcriptional regulation of Oct4 and Nanog expression via their promoters, recent genome-wide analyses of the Zic-binding sites and their downstream targets indicate that Zic proteins are associated with distant regulatory elements and are the critical enhancer-priming nuclear regulators in organismal development. Chromatin-remodeling complexes such as NuRD and NURF that interact with Zic proteins have been shown to participate in Zic-mediated enhancer regulation.

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Zic1 is a Transcriptional Repressor Through the Lamin A/C Promoter and has an Intrinsic Repressive Domain

Cited by 4 publications

References 20 publications

The nuclear lamina is mechano-responsive to ECM elasticity in mature tissue

The nuclear lamina is mechano-responsive to ECM elasticity in mature tissue

The Nuclear Lamina: From Mechanosensing in Differentiation to Cancer Cell Migration

Role of Zic Family Proteins in Transcriptional Regulation and Chromatin Remodeling

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