BIOM 503
LIBERTY UNIVERSITY
FALL 2020
BIOM 503
LECTURE ASSIGNMENT 2 INSTRUCTIONS
Compose a paragraph-style response for the essay topics listed below. The assignment must
reflect your own understanding of the course material.
1. Compare and contrast 3 promoter motifs. Points of discussion must include how or where
the promoter motifs are found and what proteins bind to them.
2. In the first figure of “DNMT3L Connects Unmethylated Lysine 4 of Histone H3 to de
novo Methylation of DNA,” the authors determined that the DNMT3L protein interacts
with several histone proteins. Using Figure 2a and b, explain how each of the 4 histones
interact with DNMT3L.
3. Briefly describe how the association of DNMT1 with the following proteins ensures that
it will be found on hemimethylated DNA:
a) UHRF1
b) PCNA
Submit your assignment by 11:59 p.m. (ET) on Sunday of Module/Week 1.
3. DNMT1 is an enzyme that is responsible for the transfer of methyl group to cytosine
nucleotides in DNA and this process is defined as the DNA Methyltion. DNA methylation
is responsible for the regulation of chromatin structure and gene expression and is part
of the DNA modification process. DNA methylation occurs at cytosine-C5 in CpG
dinucleotides in humans. DNMT1 is one part of a family of three in DNMT, which are
DNMT1, DNMT2 and DNMT3. DNMT1 has strong preference for semi methylated
substrates and plays an important role in maintaining the pattern of DNA methylation
during cell division.
DNMT1 interacts and binds with a trimer protein called proliferating cell nuclear antigen
(PCNA). PCNA is a cofactor of DNA polymerase that hangs on DNA during replication.
PCNA targets and transfers DNMT1 to the replication fork where maintenance needs to
occur. Hemimethylated location on the DNA is where the double stranded DNA
duplicates where we have a new strands on each of the template strands, the leading
and lagging strand. These newly duplicated strands are hemimethylated because the
the old stand is methylated whereas the new strand is not methylated. The
hemimethylated DNA strands attract DNMT1 where it interacts with PCNA that is
located on the replication fork.
However, PCNA itself is not enough to recruit DNMT1 and requires another protein
named UHRF1. UHRF1 is a nuclear protein that recognizes hemi-CpG. UHRF1 plays
an important role in maintinang DNA methylation. It has five conserved domain: a
BIOM 503
ubiquitin-like domain (UBl), a tandem tudor domain (TTD), a plant homeodomain (phD),
a SET and RING associated (SRA) domain, and a Really Interesting New Gene (RING)
domain (Tollefsbol,1). After PCNA targeting and moving DNMT1 to the replication fork,
UHRF1 interacts with DNMT1 and directs it to hemimethylated CpG sites that needs to
be replicated. It directs it as the tandem tudor domain and the plant homeodomain in the
UHRF1 work to identify the histone h3 trimethylated at lysine 9 (h3K- 9me3) mark. The
SRA domain is responsible for directing DNMT1 to the new DNA substrates and binds
to hemimethylated DNA. The DNA pattern will be conserved before and after
methylation regardless of the replication proccess.
Refrences:
1. Tollefsbol, Trygve O. Handbook of Epigenetics: the New Molecular and Medical
Genetics. Elsevier Academic Press, 2017.
