Life Sciences Research for Lifelong Health

Gavin Kelsey

Research Summary

As well as genetic information, the egg and sperm also contribute epigenetic annotations that may influence gene activity after fertilisation. These annotations may be direct modifications of the DNA bases or of the proteins around which the DNA is wrapped into chromatin. Our goal is to understand whether, through epigenetics, factors such as a mother’s age or diet have consequences on the health of a child.
 
We examine how epigenetic states are set up in oocytes – or egg cells – and influence gene expression in the embryo. For example, repressive chromatin marks in oocytes lead to long-term silencing of genes inherited from the mother, particularly in cells that will form the placenta. We are also interested in how variations in DNA methylation come about in oocytes and whether we can use this variation as a marker for oocyte quality and embryo potential. To investigate these questions, we develop methods to profile epigenetic information in very small numbers of cells or even in single cells.

Latest Publications

The role and mechanisms of DNA methylation in the oocyte.
Sendžikaitė G, Kelsey G

Epigenetic information in the mammalian oocyte has the potential to be transmitted to the next generation and influence gene expression; this occurs naturally in the case of imprinted genes. Therefore, it is important to understand how epigenetic information is patterned during oocyte development and growth. Here, we review the current state of knowledge of de novo DNA methylation mechanisms in the oocyte: how a distinctive gene-body methylation pattern is created, and the extent to which the DNA methylation machinery reads chromatin states. Recent epigenomic studies building on advances in ultra-low input chromatin profiling methods, coupled with genetic studies, have started to allow a detailed interrogation of the interplay between DNA methylation establishment and chromatin states; however, a full mechanistic description awaits.

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Essays in biochemistry, , 1744-1358, , 2019

PMID: 31782490

Endogenous retroviral insertions drive non-canonical imprinting in extra-embryonic tissues.
Hanna CW, Pérez-Palacios R, Gahurova L, Schubert M, Krueger F, Biggins L, Andrews S, Colomé-Tatché M, Bourc'his D, Dean W, Kelsey G

Genomic imprinting is an epigenetic phenomenon that allows a subset of genes to be expressed mono-allelically based on the parent of origin and is typically regulated by differential DNA methylation inherited from gametes. Imprinting is pervasive in murine extra-embryonic lineages, and uniquely, the imprinting of several genes has been found to be conferred non-canonically through maternally inherited repressive histone modification H3K27me3. However, the underlying regulatory mechanisms of non-canonical imprinting in post-implantation development remain unexplored.

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Genome biology, 20, 1474-760X, 225, 2019

PMID: 31665063

DNA methylation and mRNA expression of imprinted genes in blastocysts derived from an improved in vitro maturation method for oocytes from small antral follicles in polycystic ovary syndrome patients.
Saenz-de-Juano MD, Ivanova E, Romero S, Lolicato F, Sánchez F, Van Ranst H, Krueger F, Segonds-Pichon A, De Vos M, Andrews S, Smitz J, Kelsey G, Anckaert E

Does imprinted DNA methylation or imprinted gene expression differ between human blastocysts from conventional ovarian stimulation (COS) and an optimized two-step IVM method (CAPA-IVM) in age-matched polycystic ovary syndrome (PCOS) patients?

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Human reproduction (Oxford, England), 34, 1460-2350, 1640-1649, 2019

PMID: 31398248

Group Members

Latest Publications

The role and mechanisms of DNA methylation in the oocyte.

Sendžikaitė G, Kelsey G

Essays in biochemistry
1744-1358: (2019)

PMID: 31782490

Endogenous retroviral insertions drive non-canonical imprinting in extra-embryonic tissues.

Hanna CW, Pérez-Palacios R, Gahurova L

Genome biology
20 1474-760X:225 (2019)

PMID: 31665063

A DNMT3A PWWP mutation leads to methylation of bivalent chromatin and growth retardation in mice.

Sendžikaitė G, Hanna CW, Stewart-Morgan KR

Nature communications
10 2041-1723:1884 (2019)

PMID: 31015495

Genomic Imprinting and Physiological Processes in Mammals.

Tucci V, Isles AR, Kelsey G

Cell
176 1097-4172:952-965 (2019)

PMID: 30794780

Genome-Scale Oscillations in DNA Methylation during Exit from Pluripotency.

Rulands S, Lee HJ, Clark SJ

Cell systems
2405-4712: (2018)

PMID: 30031774

Epigenetic regulation in development: is the mouse a good model for the human?

Hanna CW, Demond H, Kelsey G

Human reproduction update
1460-2369: (2018)

PMID: 29992283

scNMT-seq enables joint profiling of chromatin accessibility DNA methylation and transcription in single cells.

Clark SJ, Argelaguet R, Kapourani CA

Nature communications
9 2041-1723:781 (2018)

PMID: 29472610

MLL2 conveys transcription-independent H3K4 trimethylation in oocytes.

Hanna CW, Taudt A, Huang J

Nature structural & molecular biology
25 1545-9985:73-82 (2018)

PMID: 29323282

Cultured bovine embryo biopsy conserves methylation marks from original embryo.

Fonseca Balvís N, Garcia-Martinez S, Pérez-Cerezales S

Biology of reproduction
97 1529-7268:189-196 (2017)

PMID: 29044423

Single-cell epigenomics: Recording the past and predicting the future.

Kelsey G, Stegle O, Reik W

Science (New York, N.Y.)
358 1095-9203:69-75 (2017)

PMID: 28983045

DNA Methylation in Embryo Development: Epigenetic Impact of ART (Assisted Reproductive Technologies).

Canovas S, Ros.s PJ, Kelsey G

BioEssays : news and reviews in molecular, cellular and developmental biology
1521-1878: (2017)

PMID: 28940661