Cell‐type‐specific interactions at regulatory motifs in the first intron of the lamin A gene

Arora, Puneeta; Muralikrishna, Bh; Parnaik, Veena K.

doi:10.1016/j.febslet.2004.05.019

Cited by 10 publications

(4 citation statements)

References 32 publications

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“…There are also other regulatory motifs in the LMNA promoter binding the transcription factors Sp1/3, c-Jun, and c-Fos, and the transcriptional coactivator CREB-binding protein Janaki Ramaiah and Parnaik 2006). Within the first intron of LMNA there are binding sites for the transcription factors, hepatocyte nuclear factor-3␤ and retinoic X receptor ␤ (Arora et al 2004). Recently, lamins A/C have been identified as p53 targets in mitomycin C-treated HCT116 colon carcinoma cells (RahmanRoblick et al 2007).…”

Section: Nuclear Lamin Expression During Development and Differentiationmentioning

confidence: 99%

Nuclear lamins: major factors in the structural organization and function of the nucleus and chromatin

Dechat

Pfleghaar²,

Sengupta³

et al. 2008

Genes Dev.

870

879

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Over the past few years it has become evident that the intermediate filament proteins, the types A and B nuclear lamins, not only provide a structural framework for the nucleus, but are also essential for many aspects of normal nuclear function. Insights into lamin-related functions have been derived from studies of the remarkably large number of disease-causing mutations in the human lamin A gene. This review provides an up-to-date overview of the functions of nuclear lamins, emphasizing their roles in epigenetics, chromatin organization, DNA replication, transcription, and DNA repair. In addition, we discuss recent evidence supporting the importance of lamins in viral infections.In eukaryotic cells, chromatin is tightly packed in a highly organized fashion within a nucleus that is composed of two main compartments: the nucleoplasm and the nuclear envelope (NE). There are also subcompartments in the nucleus containing factors involved in essential nuclear functions such as DNA replication, transcription, and RNA splicing (Prasanth and Spector 2006;Spector 2006). The NE separates nuclear functions from cytoplasmic functions and at its inner surface it provides a docking site for chromatin. The major structural elements of the NE are the inner nuclear membrane (INM), the outer nuclear membrane (ONM), the nuclear pore complexes (NPCs), and the nuclear lamina. The lamina is comprised of a complex meshwork of proteins closely associated with the INM and attached to the periphery of NPCs and to chromatin (Fawcett 1966;Patrizi and Poger 1967;Aaronson and Blobel 1975). The main constituents of the lamina are the type V intermediate filament (IF) proteins, the nuclear lamins. Lamins are also found, in lower concentrations, distributed throughout the nucleoplasm. The organization of lamins at the nuclear periphery as well as within the nucleoplasm is influenced by numerous lamin-binding proteins (Dorner et al. 2007;Schirmer and Foisner 2007;Wagner and Krohne 2007).This review focuses on the role of nuclear lamins in the organization and regulation of chromatin in the interphase nucleus-specifically, the involvement of lamins in essential processes such as transcription, DNA replication, DNA repair, and various epigenetic phenomena involved in the regulation of euchromatin-heterochromatin transitions. Emphasis is also placed on the remarkable array of disease-causing mutations in the human lamin A gene, from which many of the most recent insights into lamin functions have been derived. In addition, we also discuss emerging ideas regarding the roles of lamins in viral infections. General properties of the nuclear laminsNuclear lamins were initially described as the major protein components of detergent-high salt resistant "lamina" fractions of rat liver and chicken erythrocyte nuclei (Aaronson and Blobel 1975;Gerace et al. 1978). Subsequently it was shown that they are members of the IF protein family (Aebi et al. 1986;Goldman et al. 1986;McKeon et al. 1986). Lamin genes are found in all metazoa examined to date, but are...

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Section: Nuclear Lamin Expression During Development and Differentiationmentioning

confidence: 99%

Nuclear lamins: major factors in the structural organization and function of the nucleus and chromatin

Dechat

Pfleghaar²,

Sengupta³

et al. 2008

Genes Dev.

870

879

View full text Add to dashboard Cite

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“…In contrast, the germline-specific lamin C2 uses a different transcription promoter and an alternative exon 1 that are embedded in the first intron of lamin A/C. A 420 base region within Lmna intron 1 has been identified to regulate the cell type-specific expression of lamin C2 45. This region contains an AT rich motif that pairs with the hepatocyte nuclear factor-3β of the winged helix/foxhead transcription factor and another that binds the retinoic X receptor proteins 46.…”

Section: Regulation Of Lmna Splicingmentioning

confidence: 99%

Normal and aberrant splicing ofLMNA

2014

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The LMNA gene gives rise to at least three isoforms (lamin A, C, lamin AΔ10) as a result of normal alternative splicing, regulated by cis- and trans-acting regulatory factors, as well as the 5' and 3' untranslated regions of the gene. The two main isoforms, lamin A and C, are constitutive components of the fibrous nuclear lamina and have diverse physiological roles, ranging from mechanical nuclear membrane maintenance to gene regulation. The clinical spectrum of diseases (called 'laminopathies') caused by LMNA mutations is broad, including at least eight well-characterised phenotypes, some of which are confined to the skeletal muscles or skin, while others are multisystemic. This review discusses the different alternatively spliced isoforms of LMNA and the regulation of LMNA splicing, as well as the subgroup of mutations that affect splicing of LMNA pre-mRNA, and also seeks to bridge the mis-splicing of LMNA at transcript level and the resulting clinical phenotypes. Finally, we discuss the manipulation of LMNA splicing by splice-switching antisense oligonucleotides and its therapeutic potential for the treatment of some laminopathies.

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“…It is encoded by the LMNA gene on chromosome 1q21, which is transcribed as different splicing products including lamin A, lamin C, lamin A Δ10 and lamin C2 (Arora et al , 2004). …”

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confidence: 99%

Different prelamin A forms accumulate in human fibroblasts: a study in experimental models and progeria

Dominici¹,

Fiori²,

Magnani³

et al. 2009

Eur J Histochem

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Lamin A is a component of the nuclear lamina mutated in a group of human inherited disorders known as laminopathies. Among laminopathies, progeroid syndromes and lipodystrophies feature accumulation of prelamin A, the precursor protein which, in normal cells, undergoes a multi-step processing to yield mature lamin A. It is of utmost importance to characterize the prelamin A form accumulated in each laminopathy, since existing evidence shows that drugs acting on protein processing can improve some pathological aspects. We report that two antibodies raised against differently modified prelamin A peptides show a clear specificity to full-length prelamin A or carboxymethylated farnesylated prelamin A, respectively. Using these antibodies, we demonstrated that inhibition of the prelamin A endoprotease ZMPSTE24 mostly elicits accumulation of full-length prelamin A in its farnesylated form, while loss of the prelamin A cleavage site causes accumulation of carboxymethylated prelamin A in progeria cells. These results suggest a major role of ZMPSTE24 in the first prelamin A cleavage step.

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Cell‐type‐specific interactions at regulatory motifs in the first intron of the lamin A gene

Cited by 10 publications

References 32 publications

Nuclear lamins: major factors in the structural organization and function of the nucleus and chromatin

Nuclear lamins: major factors in the structural organization and function of the nucleus and chromatin

Normal and aberrant splicing ofLMNA

Different prelamin A forms accumulate in human fibroblasts: a study in experimental models and progeria

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