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Integration of Biochemical and Mechanical Signals at the Nuclear Periphery: Impacts on Skin Development and Disease

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Epigenetic Regulation of Skin Development and Regeneration

Part of the book series: Stem Cell Biology and Regenerative Medicine ((STEMCELL))

Abstract

During skin development and keratinocyte differentiation, the nucleus undergoes characteristic changes in shape, size, and transcriptional output. Many of these changes are regulated by the interface between the nuclear interior and the inner nuclear membrane, a region called the nuclear lamina. The nuclear lamina is composed of a meshwork of the nuclear lamins, which interact with integral inner nuclear membrane proteins, and the associated chromatin. Studies in the last decade have revealed a view of the nuclear lamina as a hub for biochemical and mechanical inputs. In this chapter, we will discuss how the structure and organization of the nucleus allows biochemical and mechanical signals to regulate gene expression, genome integrity, cell and tissue level mechanics, and disease in the context of skin homeostasis and regeneration.

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Abbreviations

AJs:

Adherens junctions

APC:

Adenomatous polyposis coli

BAF:

Barrier-to-autointegration factor

ChIP-seq:

Chromatin immunoprecipitation sequencing

DDR:

DNA damage response

DSB:

Double-strand break

ECM:

Extracellular Matrix

EDC:

Epidermal differentiation complex

GA repeat:

Guanine-adenine repeat

H2K9me2/3:

Di- or trimethylation of lysine 9 on histone H2

H3K27me3:

Trimethylation of lysine 27 on histone H3

HDAC:

Histone deacetylase

HGPS:

Hutchinson-Gilford Progeria Syndrome

Hi-C:

High-throughput chromosome capture

IFE:

Interfollicular epidermis

INM:

Inner nuclear membrane

LEM:

LAP2, emerin and MAN1

ONM:

Outer nuclear membrane

LAD:

Lamina associated domain

LAP1:

Lamina-associated polypeptide 1

LAP2:

Lamina-associated polypeptide 2

LBR:

Lamin B receptor

LINC:

Linker of Nucleoskeleton and Cytoskeleton

MEF:

Mouse embryonic fibroblast

RGD:

Arginylglycylaspartic acid

TAN lines:

Transmembrane actin-associated nuclear lines

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Authors and Affiliations

  1. Department of Cell Biology, Yale School of Medicine, New Haven, CT, USA

    Rachel M. Stewart & Megan C. King

  2. Department of Dermatology, Yale School of Medicine, New Haven, CT, USA

    Valerie Horsley

  3. Department of Molecular, Cell and Developmental Biology, Yale University, New Haven, CT, USA

    Valerie Horsley

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  1. Rachel M. Stewart
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  2. Megan C. King
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  3. Valerie Horsley
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Correspondence to Megan C. King or Valerie Horsley .

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Editors and Affiliations

  1. Centre for Skin Sciences, University of Bradford, Bradford, UK

    Vladimir A. Botchkarev

  2. Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Sarah E. Millar

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Stewart, R.M., King, M.C., Horsley, V. (2018). Integration of Biochemical and Mechanical Signals at the Nuclear Periphery: Impacts on Skin Development and Disease. In: Botchkarev, V., Millar, S. (eds) Epigenetic Regulation of Skin Development and Regeneration. Stem Cell Biology and Regenerative Medicine. Humana Press, Cham. https://doi.org/10.1007/978-3-319-16769-5_11

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