HR (Human Reproduction) Lecture Notes: Genomic
Imprinting
Imprinting protects against parthogenesis and transposons
● Gynogenote can give teratoma
Imprinted genes lie in clusters
Either too much maternal or paternal chromosome
● Extra paternal -> overgrowth
● Extra maternal -> growth restricted (more maternal stress)
15q11-13
● Angelman syndrome, lack of maternal
● Prader-Willi syndromw, lack of paternal
Epigenetic modifications
● Methylation (at CpG dinucleotides)
○ Effectors
◆ Writers: DNMTs (DNA MethylTransferases)
◆ De novo: DNMT3A,B
◆ Maintenance: DNMT1
◆ Readers: Methyl binding proteins
◆ Erasers: passive or active (Tet 1-3 enzymes) demethylation
○ CpG islands are usually overlapping promoters
○ Lifecycle
◆ Fertillisation: demethylation (but not of maternal and paternal
imprinted genes)
◆ Blastocyst: remethylation
◆ ICM has more methylation than TE
◆ Proteins protect imprinted genes in de and remethylation
◆ PGCs: passive then active de then remethylation
◆ Sperm remethylation before birth
◆ Oocyte remethylation at follicle activation (before
ovulation)
● Histone modifications
○ Acetylation, methylation, phosphorylation, deimination,
ubiquitination
○ Active histone modification (e.g. H3K4me3)
○ Repressive histone modification (e.g H3K27me3)
● Not usually inherited (since wiped in PGCs) but secondary epimutation
can if due to inherited gene
ICR
● Common regulatory element within a cluster of imprinted genes that
confers monoallelic gene expression
● Disorders have a gain or loss of methylation
Imprinting
Imprinting protects against parthogenesis and transposons
● Gynogenote can give teratoma
Imprinted genes lie in clusters
Either too much maternal or paternal chromosome
● Extra paternal -> overgrowth
● Extra maternal -> growth restricted (more maternal stress)
15q11-13
● Angelman syndrome, lack of maternal
● Prader-Willi syndromw, lack of paternal
Epigenetic modifications
● Methylation (at CpG dinucleotides)
○ Effectors
◆ Writers: DNMTs (DNA MethylTransferases)
◆ De novo: DNMT3A,B
◆ Maintenance: DNMT1
◆ Readers: Methyl binding proteins
◆ Erasers: passive or active (Tet 1-3 enzymes) demethylation
○ CpG islands are usually overlapping promoters
○ Lifecycle
◆ Fertillisation: demethylation (but not of maternal and paternal
imprinted genes)
◆ Blastocyst: remethylation
◆ ICM has more methylation than TE
◆ Proteins protect imprinted genes in de and remethylation
◆ PGCs: passive then active de then remethylation
◆ Sperm remethylation before birth
◆ Oocyte remethylation at follicle activation (before
ovulation)
● Histone modifications
○ Acetylation, methylation, phosphorylation, deimination,
ubiquitination
○ Active histone modification (e.g. H3K4me3)
○ Repressive histone modification (e.g H3K27me3)
● Not usually inherited (since wiped in PGCs) but secondary epimutation
can if due to inherited gene
ICR
● Common regulatory element within a cluster of imprinted genes that
confers monoallelic gene expression
● Disorders have a gain or loss of methylation
