Silencing of transgene expression in mammalian cells by DNA methylation and histone modifications in gene therapy perspective

ABSTRACT

DNA methylation and histone modifications are vital in maintaining genomic stability and modulating cellular functions in mammalian cells. These two epigenetic modifications are the most common gene regulatory systems known to spatially control gene expression. Transgene silencing by these two mechanisms is a major challenge to achieving effective gene therapy for many genetic conditions. The implications of transgene silencing caused by epigenetic modifications have been extensively studied and reported in numerous gene delivery studies. This review highlights instances of transgene silencing by DNA methylation and histone modification with specific focus on the role of these two epigenetic effects on the repression of transgene expression in mammalian cells from integrative and non-integrative based gene delivery systems in the context of gene therapy. It also discusses the prospects of achieving an effective and sustained transgene expression for future gene therapy applications.

KEYWORDS:

• DNA methylation
• histone modification
• transgene repression
• gene therapy

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the Ministry of Science and Technology and Innovation (MOSTI) Malaysia grant number [02-01-04-SF1838] and Ministry of Higher Education Malaysia grant number [FRGS/1/2016/SKK09/UPM/02/3].

Notes on contributors

Suleiman Yusuf Alhaji

Suleiman Yusuf Alhaji was born in Misau, Bauchi State Nigeria. He obtained his PhD from the Faculty of Medicine and Health Sciences, Universiti Putra Malaysia. He is currently a full time lecturer/researcher at the department of Human Anatomy, College of Medical Sciences, Abubakar Tafawa Balewa University, Bauchi, Nigeria.

Siew Ching Ngai

Siew Ching Ngai is an Assistant Professor at the University of Nottingham Malaysia Campus. She obtained her PhD in the field of Molecular Medicine. Her research interests are in the field of gene delivery, epigenetics, stem cells and cancer research. She is a member of the Royal Society of Biology and the Ambassador of the European Association of Cancer Research.

Syahril Abdullah

Syahril Abdullah is a Deputy Director at Institute of Bioscience and a faculty member at the Faculty of Medicine & Health Sciences, Universiti Putra Malaysia, where he is currently an Associate Professor. He earned his DPhil from University of Oxford, UK. His primary research interest is in the field of gene therapy, focusing on ways to extend the duration of therapeutic gene expression. He is an honorary member of the Young Scientist Network - Academy of Sciences Malaysia.