scholarly journals Effect of SUV39H1 Histone Methyltransferase Knockout on Expression of Differentiation-Associated Genes in HaCaT Keratinocytes

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2628
Author(s):  
Barbara Sobiak ◽  
Wiesława Leśniak
Keyword(s):  
Gene Expression ◽  
Skin Diseases ◽  
Human Keratinocytes ◽  
Histone Methyltransferase ◽  
Epidermal Differentiation ◽  
Gene Encoding ◽  
Epidermal Differentiation Complex ◽  
Expression Of Genes ◽  
State Dependent ◽  
Genomic Locations

Keratinocytes undergo a complex differentiation process, coupled with extensive changes in gene expression through which they acquire distinctive features indispensable for cells that form the external body barrier—epidermis. Disturbed epidermal differentiation gives rise to multiple skin diseases. The involvement of epigenetic factors, such as DNA methylation or histone modifications, in the regulation of epidermal gene expression and differentiation has not been fully recognized yet. In this work we performed a CRISPR/Cas9-mediated knockout of SUV39H1, a gene-encoding H3K9 histone methyltransferase, in HaCaT cells that originate from spontaneously immortalized human keratinocytes and examined changes in the expression of selected differentiation-specific genes located in the epidermal differentiation complex (EDC) and other genomic locations by RT-qPCR. The studied genes revealed a diverse differentiation state-dependent or -independent response to a lower level of H3K9 methylation. We also show, by means of chromatin immunoprecipitation, that the expression of genes in the LCE1 subcluster of EDC was regulated by the extent of trimethylation of lysine 9 in histone H3 bound to their promoters. Changes in gene expression were accompanied by changes in HaCaT cell morphology and adhesion.

scholarly journals PML Regulates the Epidermal Differentiation Complex and Skin Morphogenesis during Mouse Embryogenesis

Genes ◽  
2020 ◽  
Vol 11 (10) ◽  
pp. 1130
Author(s):  
Anna Połeć ◽  
Alexander D. Rowe ◽  
Pernille Blicher ◽  
Rajikala Suganthan ◽  
Magnar Bjørås ◽  
...  
Keyword(s):  
Gene Expression ◽  
Developmental Stages ◽  
Expression Patterns ◽  
Growth Control ◽  
Wild Type Mouse ◽  
Global Gene Expression ◽  
Mouse Embryos ◽  
Epidermal Differentiation ◽  
Envelope Gene ◽  
Epidermal Differentiation Complex

The promyelocytic leukemia (PML) protein is an essential component of nuclear compartments called PML bodies. This protein participates in several cellular processes, including growth control, senescence, apoptosis, and differentiation. Previous studies have suggested that PML regulates gene expression at a subset of loci through a function in chromatin remodeling. Here we have studied global gene expression patterns in mouse embryonic skin derived from Pml depleted and wild type mouse embryos. Differential gene expression analysis at different developmental stages revealed a key role of PML in regulating genes involved in epidermal stratification. In particular, we observed dysregulation of the late cornified envelope gene cluster, which is a sub-region of the epidermal differentiation complex. In agreement with these data, PML body numbers are elevated in basal keratinocytes during embryogenesis, and we observed reduced epidermal thickness and defective hair follicle development in PML depleted mouse embryos.

scholarly journals The Role of the Histone Methyltransferase PfSET10 in Antigenic Variation by Malaria Parasites: a Cautionary Tale

mSphere ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Che J. Ngwa ◽  
Mackensie R. Gross ◽  
Jean-Pierre Musabyimana ◽  
Gabriele Pradel ◽  
Kirk W. Deitsch
Keyword(s):  
Gene Expression ◽  
New Technologies ◽  
Antigenic Variation ◽  
Histone Methyltransferase ◽  
Research Focus ◽  
Gene Encoding ◽  
Content Type ◽  
High Profile ◽  
Key Enzyme ◽  
Parasite Viability

ABSTRACT The virulence of the malaria parasite Plasmodium falciparum is due in large part to its ability to avoid immune destruction through antigenic variation. This results from changes in expression within the multicopy var gene family that encodes the surface antigen P. falciparum erythrocyte protein one (PfEMP1). Understanding the mechanisms underlying this process has been a high-profile research focus for many years. The histone methyltransferase PfSET10 was previously identified as a key enzyme required both for parasite viability and for regulating var gene expression, thus making it a prominent target for developing antimalarial intervention strategies and the subject of considerable research focus. Here, however, we show that disruption of the gene encoding PfSET10 is not lethal and has no effect on var gene expression, in sharp contrast with previously published reports. The contradictory findings highlight the importance of reevaluating previous conclusions when new technologies become available and suggest the possibility of a previously unappreciated plasticity in epigenetic gene regulation in P. falciparum. IMPORTANCE The identification of specific epigenetic regulatory proteins in infectious organisms has become a high-profile research topic and a focus for several drug development initiatives. However, studies that define specific roles for different epigenetic modifiers occasionally report differing results, and we similarly provide evidence regarding the histone methyltransferase PfSET10 that is in stark contrast with previously published results. We believe that the conflicting results, rather than suggesting erroneous conclusions, instead reflect the importance of revisiting previous conclusions using newly developed methodologies, as well as caution in interpreting seemingly contrary results in fields that are known to display considerable plasticity, for example metabolism and epigenetics.

scholarly journals Epidermal differentiation complex (locus 1q21) gene expression in head and neck cancer and normal mucosa

2014 ◽  
Vol 52 (2) ◽  
pp. 79-89 ◽  
Author(s):  
Tomasz Tyszkiewicz ◽  
Michal Jarzab ◽  
Cezary Szymczyk ◽  
Monika Kowal ◽  
Jolanta Krajewska ◽  
...  
Keyword(s):  
Gene Expression ◽  
Head And Neck Cancer ◽  
Head And Neck ◽  
Neck Cancer ◽  
Normal Mucosa ◽  
Epidermal Differentiation ◽  
Epidermal Differentiation Complex ◽  
Complex Locus

scholarly journals Single-cell transcriptomics defines keratinocyte differentiation in avian scutate scales

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Julia Lachner ◽  
Florian Ehrlich ◽  
Matthias Wielscher ◽  
Matthias Farlik ◽  
Marcela Hermann ◽  
...  
Keyword(s):  
Gene Expression ◽  
Single Cell ◽  
Terminal Differentiation ◽  
Epidermal Differentiation ◽  
Keratinocyte Differentiation ◽  
Epidermal Keratinocytes ◽  
Scale Type ◽  
Epidermal Differentiation Complex ◽  
Evolutionarily Conserved ◽  
Beta Proteins

AbstractThe growth of skin appendages, such as hair, feathers and scales, depends on terminal differentiation of epidermal keratinocytes. Here, we investigated keratinocyte differentiation in avian scutate scales. Cells were isolated from the skin on the legs of 1-day old chicks and subjected to single-cell transcriptomics. We identified two distinct populations of differentiated keratinocytes. The first population was characterized by mRNAs encoding cysteine-rich keratins and corneous beta-proteins (CBPs), also known as beta-keratins, of the scale type, indicating that these cells form hard scales. The second population of differentiated keratinocytes contained mRNAs encoding cysteine-poor keratins and keratinocyte-type CBPs, suggesting that these cells form the soft interscale epidermis. We raised an antibody against keratin 9-like cysteine-rich 2 (KRT9LC2), which is encoded by an mRNA enriched in the first keratinocyte population. Immunostaining confirmed expression of KRT9LC2 in the suprabasal epidermal layers of scutate scales but not in interscale epidermis. Keratinocyte differentiation in chicken leg skin resembled that in human skin with regard to the transcriptional upregulation of epidermal differentiation complex genes and genes involved in lipid metabolism and transport. In conclusion, this study defines gene expression programs that build scutate scales and interscale epidermis of birds and reveals evolutionarily conserved keratinocyte differentiation genes.

scholarly journals Acute Systemic Inflammatory Response Alters Transcription Profile of Genes Related to Immune Response and Ca2+ Homeostasis in Hippocampus; Relevance to Neurodegenerative Disorders

2020 ◽  
Vol 21 (21) ◽  
pp. 7838
Author(s):  
Grzegorz A. Czapski ◽  
Yuhai Zhao ◽  
Walter J. Lukiw ◽  
Joanna B. Strosznajder
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Inflammatory Response ◽  
Histone Deacetylases ◽  
Expression Patterns ◽  
Enrichment Analysis ◽  
Systemic Inflammatory Response ◽  
Lipocalin 2 ◽  
Gene Encoding ◽  
Expression Of Genes

Acute systemic inflammatory response (SIR) triggers an alteration in the transcription of brain genes related to neuroinflammation, oxidative stress and cells death. These changes are also characteristic for Alzheimer’s disease (AD) neuropathology. Our aim was to evaluate gene expression patterns in the mouse hippocampus (MH) by using microarray technology 12 and 96 h after SIR evoked by lipopolysaccharide (LPS). The results were compared with microarray analysis of human postmortem hippocampal AD tissues. It was found that 12 h after LPS administration the expression of 231 genes in MH was significantly altered (FC > 2.0); however, after 96 h only the S100a8 gene encoding calgranulin A was activated (FC = 2.9). Gene ontology enrichment analysis demonstrated the alteration of gene expression related mostly to the immune-response including the gene Lcn2 for Lipocalin 2 (FC = 237.8), involved in glia neurotoxicity. The expression of genes coding proteins involved in epigenetic regulation, histone deacetylases (Hdac4,5,8,9,11) and bromo- and extraterminal domain protein Brd3 were downregulated; however, Brd2 was found to be upregulated. Remarkably, the significant increase in expression of Lcn2, S100a8, S100a9 and also Saa3 and Ch25h, was found in AD brains suggesting that early changes of immune-response genes evoked by mild SIR could be crucial in AD pathogenesis.

scholarly journals The human Cx26-D50A and Cx26-A88V mutations causing keratitis-ichthyosis-deafness syndrome display increased hemichannel activity

2013 ◽  
Vol 304 (12) ◽  
pp. C1150-C1158 ◽  
Author(s):  
Pallavi V. Mhaske ◽  
Noah A. Levit ◽  
Leping Li ◽  
Hong-Zhan Wang ◽  
Jack R. Lee ◽  
...  
Keyword(s):  
Calcium Concentration ◽  
Skin Diseases ◽  
Human Keratinocytes ◽  
Extracellular Calcium ◽  
Membrane Current ◽  
Wild Type ◽  
Nonsyndromic Deafness ◽  
Primary Human Keratinocytes ◽  
Gene Encoding ◽  
Clinical Disorders

Mutations in the human gene encoding connexin 26 (Cx26 or GJB2) cause either nonsyndromic deafness or syndromic deafness associated with skin diseases. That distinct clinical disorders can be caused by different mutations within the same gene suggests that different channel activities influence the ear and skin. Here we use three different expression systems to examine the functional characteristics of two Cx26 mutations causing either mild (Cx26-D50A) or lethal (Cx26-A88V) keratitis-ichthyosis-deafness (KID) syndrome. In either cRNA-injected Xenopus oocytes, transfected HeLa cells, or transfected primary human keratinocytes, we show that both Cx26-D50A and Cx26-A88V form active hemichannels that significantly increase membrane current flow compared with wild-type Cx26. This increased membrane current accelerated cell death in low extracellular calcium solutions and was not due to increased mutant protein expression. Elevated mutant hemichannel currents could be blocked by increased extracellular calcium concentration. These results show that these two mutations exhibit a shared gain of functional activity and support the hypothesis that increased hemichannel activity is a common feature of human Cx26 mutations responsible for KID syndrome.

scholarly journals The Epidermis: Redox Governor of Health and Diseases

Antioxidants ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 47
Author(s):  
Yosuke Ishitsuka ◽  
Dennis R. Roop
Keyword(s):  
Skin Diseases ◽  
Protective Layer ◽  
Xenobiotic Metabolism ◽  
Epidermal Differentiation ◽  
Erythroid Cell ◽  
Permeability Barrier ◽  
Related Factor ◽  
Stratum Granulosum ◽  
Epidermal Differentiation Complex ◽  
Uppermost Layer

A functional epithelial barrier necessitates protection against dehydration, and ichthyoses are caused by defects in maintaining the permeability barrier in the stratum corneum (SC), the uppermost protective layer composed of dead cells and secretory materials from the living layer stratum granulosum (SG). We have found that loricrin (LOR) is an essential effector of cornification that occurs in the uppermost layer of SG (SG1). LOR promotes the maturation of corneocytes and extracellular adhesion structure through organizing disulfide cross-linkages, albeit being dispensable for the SC permeability barrier. This review takes psoriasis and AD as the prototype of impaired cornification. Despite exhibiting immunological traits that oppose each other, both conditions share the epidermal differentiation complex as a susceptible locus. We also review recent mechanistic insights on skin diseases, focusing on the Kelch-like erythroid cell-derived protein with the cap “n” collar homology-associated protein 1/NFE2-related factor 2 signaling pathway, as they coordinate the epidermis-intrinsic xenobiotic metabolism. Finally, we refine the theoretical framework of thiol-mediated crosstalk between keratinocytes and leukocytes in the epidermis that was put forward earlier.

scholarly journals Obesity and Race Alter Gene Expression in Skin

2020 ◽  
Author(s):  
Jeanne M. Walker ◽  
Sandra Garcet ◽  
Jose O. Aleman ◽  
Christopher E. Mason ◽  
David Danko ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cystic Fibrosis ◽  
African Americans ◽  
Normal Weight ◽  
Gene Encoding ◽  
Functional Changes ◽  
Expression Of Genes ◽  
Genes Encoding ◽  
Expression Pathways ◽  
Altered Gene

ABSTRACTObesity is accompanied by dysfunction of many organs, but effects on the skin have received little attention. We studied differences in epithelial thickness by histology and gene expression by Affymetrix gene arrays and PCR in the skin of 10 obese (BMI 35-50) and 10 normal weight (BMI 18.5-26.9) postmenopausal women paired by age and race. Epidermal thickness did not differ with obesity but the expression of genes encoding proteins associated with skin blood supply and wound healing were altered. In the obese, many gene expression pathways were broadly downregulated and subdermal fat showed pronounced inflammation. There were no changes in skin microbiota or metabolites. African American subjects differed from Caucasians with a trend to increased epidermal thickening. In obese African Americans, compared to obese Caucasians, we observed altered gene expression that may explain known differences in water content and stress response. African Americans showed markedly lower expression of the gene encoding the cystic fibrosis transmembrane regulator characteristic of the disease cystic fibrosis. The results from this preliminary study may explain the functional changes found in the skin of obese subjects and African Americans.

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