Beta-cell replication dramatically declines with age. Here, we report that the level of CENP-A, a protein required for cell division, declines precipitously with age in an islet-specific manner. CENP-A is essentially undetectable after age 29 in humans. However, exocrine cells retain CENP-A expression. The decline in islet-cell CENP-A expression is more striking in humans than in mice, where CENP-A expression continues to be detectable at low levels even in elderly mice. The mechanism by which CENP-A declines appears to be post-transcriptional, as there was no correlation between CENP-A mRNA levels and age or islet purity. This finding has implications for efforts to induce beta-cell replication as a treatment for diabetes.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3006021 | PMC |
| http://dx.doi.org/10.18632/aging.100220 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
High-resolution analysis of human centromeric chromatin.
Life Sci Alliance
April 2025
National Cancer Institute, Center for Cancer Research, Laboratory of Receptor Biology and Gene Expression, Bethesda, MD, USA
Centromeres are marked by the centromere-specific histone H3 variant CENP-A/CENH3. Throughout the cell cycle, the constitutive centromere-associated network is bound to CENP-A chromatin, but how this protein network modifies CENP-A nucleosome conformations in vivo is unknown. Here, we purify endogenous centromeric chromatin associated with the CENP-C complex across the cell cycle and analyze the structures by single-molecule imaging and biochemical assays.
View Article and Find Full Text PDFSingle-cell and bulk RNA sequencing analysis reveals CENPA as a potential biomarker and therapeutic target in cancers.
PLoS One
January 2025
Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China.
Background: Cancer remains one of the most significant public health challenges worldwide. A widely recognized hallmark of cancer is the ability to sustain proliferative signaling, which is closely tied to various cell cycle processes. Centromere Protein A (CENPA), a variant of the standard histone H3, is crucial for selective chromosome segregation during the cell cycle.
View Article and Find Full Text PDFSMR-guided molecular subtyping and machine learning model reveals novel prognostic biomarkers and therapeutic targets in non-small cell lung adenocarcinoma.
Sci Rep
January 2025
Department of Surgical Oncology II, The General Hospital of Ningxia Medical University, 804 Shengli Street, Yinchuan, Ningxia, 750004, China.
Non-small cell lung adenocarcinoma (LUAD) is a markedly heterogeneous disease, with its underlying molecular mechanisms and prognosis prediction presenting ongoing challenges. In this study, we integrated data from multiple public datasets, including TCGA, GSE31210, and GSE13213, encompassing a total of 867 tumor samples. By employing Mendelian randomization (MR) analysis, machine learning techniques, and comprehensive bioinformatics approaches, we conducted an in-depth investigation into the molecular characteristics, prognostic markers, and potential therapeutic targets of LUAD.
View Article and Find Full Text PDFTranscription of a centromere-enriched retroelement and local retention of its RNA are significant features of the CENP-A chromatin landscape.
Genome Biol
November 2024
Department of Molecular and Cell Biology, University of Connecticut, Storrs, CT, USA.
Article Synopsis
- Centromeres rely on the histone variant CENP-A and the role of surrounding DNA repeats is not fully understood, while retroelements are abundant in centromeres and may help with transcription and CENP-A integration.* -
- This study focuses on the retroelement Jockey-3 in Drosophila melanogaster, showing it is a significant part of the centromeric transcriptome and that its RNA localizes to centromeres during cell division.* -
- The research suggests that Jockey-3 inserts itself at centromeres to aid its own replication, while also supporting transcription in these areas, which could provide insights into similar mechanisms in other species.*
The white gene as a transgenesis marker for the cricket Gryllus bimaculatus.
G3 (Bethesda)
October 2024
Laboratoire de Biologie et Modélisation de la Cellule, École Normale Supérieure de Lyon, CNRS UMR5239, Université Claude Bernard Lyon 1, 9 rue du Vercors, 69007 Lyon, France.
The cricket Gryllus bimaculatus is an emerging model insect of the order Orthoptera that is used in a wide variety of biological research themes. This hemimetabolous species appears highly complementary to Drosophila and other well-established holometabolous models. To improve transgenesis applications in G.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!