CSB349H1 Lecture Notes - Lecture 7: Genomic Imprinting, Non-Coding Rna, Insulin-Like Growth Factor 2
14 May 2018
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Lecture 7(c): Methylation Dynamics & Monoallelic Expression
Pseudo-Autosomal Regions (PAR):
1. Long interspersed nuclear elements (LINE-1) are found on the X-chromosome and are
proposed to function in anchoring Xist RNA; aiding in its spreading and silencing
o PAR regions may consist of one or several (100’s) of genes that are capable of escaping
inactivation due to fewer LINE-1 repeats - Xist RNA binds less efficiently
2. Chromatin insulator protein CTCF bind and separate the transition region – region between
the escape and the inactivated region
o DNA is capable of moving and form loops from heterochromatic
regions to transcription factories where they can be transcribed
§ CTCF protein functions to prevent heterochromatin
from spreading into the escaped region
Genomic Imprinting:
• Some autosomal genes are epigenetically regulated in mammals – results in the expression
of the gene in a parent-origin specific manner:
o Gene is expressed from one allele (parental OR maternal) during early development
• Imprinted genes also do not undergo the de-methylation event after zygote formation and
will maintain their methylation pattern
o Imprinted gene play a predominant role during fetal and placental growth
ð Imprinted genes are often found in clusters and are regulated by an Imprinting Control
Region (ICR) which contains
parental-specific epigenetic markers
Germline Development:
• During the development of gametes (i.e. sperm & eggs) we have a
second round of demethylation event occurs including imprint genes
o Parental imprint will remain established in all gametes generated
Insulator Model – Genomic Imprinting:
• Two imprinted genes are involved in embryonic development are regulated
by the same enhancer element – they also have an ICR region between them:
o (1) IGF2 – paternally expressed (2) H19 – maternally expressed
Maternal Copy:
• ICR is not methylated – insulator proteins are capable of binding to ICR region
o Enhancer is capable of expressing of H19; cannot get to the enhancer site of IGF2
Paternal Copy:
• ICR is methylated – insulator protein cannot bind to ICR region
o Enhancer element is capable of expressing
IGF2
o Methylation goes beyond the ICR and into
the promotor region of H19, hence no
expression
IGF2: growth factor protein | H19: ncRNA regulate cell cycle
Document Summary
Ctcf protein functions to prevent heterochromatin from spreading into the escaped region. Genomic imprinting: some autosomal genes are epigenetically regulated in mammals results in the expression of the gene in a parent-origin specific manner, gene is expressed from one allele (parental or maternal) during early development. Imprinted genes also do not undergo the de-methylation event after zygote formation and will maintain their methylation pattern: imprinted gene play a predominant role during fetal and placental growth. Imprinted genes are often found in clusters and are regulated by an imprinting control. Germline development: during the development of gametes (i. e. sperm & eggs) we have a second round of demethylation event occurs including imprint genes, parental imprint will remain established in all gametes generated. Maternal copy: icr is not methylated insulator proteins are capable of binding to icr region, enhancer is capable of expressing of h19; cannot get to the enhancer site of igf2.
