Life Sciences Research for Lifelong Health

Gavin Kelsey

Research Summary

It is thought that epigenetic information can be programmed by environmental factors, such as diet and early life experiences, and such changes can be perpetuated long after these exposures and potentially to future generations.  Such epigenetic programming may contribute to our risk of developing disease in later life.  Imprinted genes (whose expression is determined by the parent that contributed them) are a model for how epigenetic events in gametes of one generation dictate gene activity in the next.

Our mapping of methylation of DNA in the egg, sperm and embryo suggests that this epigenetic influence may extend well beyond the small number of known imprinted genes.  Using genome-wide approaches, we are tracking the fate of DNA methylation patterns inherited from the egg and sperm, the stability of these marks throughout the lifetime and ageing, and how they affect activity of associated genes.  In particular, we are investigating whether DNA methylation in particular populations of neurons in the hypothalamus, the part of the brain that senses nutritional status to control metabolism and appetite, is altered by exposure to altered diets and may modify response to nutritional status.

The discovery that gene transcription is essential for DNA methylation and imprint establishment may help to explain how the methylation modifications in the genome of the egg may be modified by adverse environments or how imprinting is disrupted in some imprinted gene disorders.

Latest Publication:
Hira is essential for normal transcriptional regulation and efficient de novo DNA methylation during mouse oogenesis.
Nashun B, Hill PWS, Smallwood SA, Dharmalingam G, Amouroux R, Clark SJ, Sharma V, Ndjetehe E, Pelczar P, Festenstein R‎, Kelsey G, Hajkova P.
Mol Cell. 2015 AOP 5th Nov. 2015, doi:10.1016/j.molcel.2015.10.010.

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Latest Publications

Establishment and functions of DNA methylation in the germline.

Stewart KR, Veselovska L, Kelsey G

1750-192X: (2016)

PMID: 27659720

Single-cell epigenomics: powerful new methods for understanding gene regulation and cell identity.

Clark SJ, Lee HJ, Smallwood SA

Genome biology
17 1474-760X:72 (2016)

PMID: 27091476

Pervasive polymorphic imprinted methylation in the human placenta.

Hanna CW, Peñaherrera MS, Saadeh H

Genome research
1549-5469: (2016)

PMID: 26769960

Parallel single-cell sequencing links transcriptional and epigenetic heterogeneity.

Angermueller C, Clark SJ, Lee HJ

Nature methods
1548-7105: (2016)

PMID: 26752769

Keeping methylation at bay.

Kelsey G

Nature genetics
47 1546-1718:427-8 (2015)

PMID: 25916897

Epigenetics: Cellular memory erased in human embryos.

Reik W,Kelsey G

511 1476-4687:540-1 (2014)

PMID: 25079550

Single-cell genome-wide bisulfite sequencing for assessing epigenetic heterogeneity.

Smallwood SA,Lee HJ,Angermueller C,Krueger F,Saadeh H,Peat J,Andrews SR,Stegle O,Reik W,Kelsey G

Nature methods
11 1548-7105:817-20 (2014)

PMID: 25042786

The specification of imprints in mammals.

Hanna CW,Kelsey G

113 1365-2540:176-83 (2014)

PMID: 24939713