Chromatin changes induced by nuclear lamina in embryonic stem cell

• Main Author: Siah, Chia Keng
• Other Authors: Colin Stewart
• Format: Final Year Project
• Language: English
• Published: 2016
• Subjects: DRNTU::Science
• Online Access: http://hdl.handle.net/10356/67170
• Institution: Nanyang Technological University

The Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder caused by a mutation in the LMNA gene, which leads to the premature ageing of affected children. This mutation triggers the production of progerin, a truncated form of the lamin A protein. Progerin has recently been shown to trigger the loss of the heterochromatin marker H3K27me3, and the premature senescence of human fibroblasts. However, little is known as to how progerin affects chromatin organization, and whether these changes are shared across different cell lineages. In this study, we show that progerin is also able to induce chromatin changes in embryonic stem cells, thereby demonstrating that progerin effects on chromatin can be reproduced in cells with very different chromatin and nuclear lamina composition. Progerin induced significant increase in the levels of the heterochromatin marker H3K9me3 in embryonic stem cells, without affecting their pluripotency. In addition, we show that progerin did so without affecting the levels of Lap2α and senescence-associated loss of protein lamin B1. These findings provide novel insights into the regulation of chromatin organization by the nuclear lamina, and the pathophysiology underlying HGPS.