presented by HAFIZ M WASEEM university of education LAHORE Pakistan i am from mailsi vehari and studied in lahore bsc in science college multan msc from lahore

1. HAFIZ M WASEEM
UNIVERSITY OF
EDUCATION LAHORE

2. ADVANCED
MOLECULAR
BIOLOGY
DNA MODIFICATIONS

3. EPIGENETICS
Epigenetics refers to a variety of processes that have heritable effects on
gene expression programs without changes in DNA sequence.

4. NUCLEOSOME AND
CHROMATIN
• Dimers of Histones H2A, H2B, H3, H4
• Around which 146 base pairs of DNA are wrapped.
• H1 linker histone stabilizes the assembly of the octameric core into chromatin-specific higher-
order structures.
• In addition to nucleosomes, the chromatin fiber contains a large variety of additional accessory
proteins
• numerous histone variants that are not randomly distributed in chromatin but are expressed in
developmentally restricted and cell type specific patterns. The yeast and mammalian
centromeres contain a variant of histone H3, Cse4/CENP-A, that was found to be essential for
centromere assembly and function.
• Likewise, H2A.Z, a variant of histone H2A, is shown to be required for one or more essential
roles in chromatin structure that cannot be replaced by bona fide histone H2A.

5. Histones are rich in lysin and Arginine residues
The amino-terminal portion of the core histones contains a flexible
and highly basic tail region, the target of several types of post-
translational modifications.
Crystallographic analysis of the nucleosome has shown that the
histone tails are external to the core structure and are therefore
accessible for protein-protein interactions

6. MODIFICATIONS IN
HISTONE
Acetylation-Deactylation
Methylation
Phosphorylation
Two of the covalent modifications affecting the tails, acetylation and
phosphorylation, have been shown to be reversible. Consequently, if
the presence of a modification influences transcription in a particular
way, its removal may have the opposing effect.

7. ACETYLATION-
DEACTYLATION
Acetylation is the one so far more thoroughly analysed [21].
The histones amino termini lysines undergo acetylation-deacetylation
switches depending on the different physiological conditions.
The balance between these modifications is achieved through the action
of enzymes dubbed histone acetyltransferases (HATs) and histone
deacetyltransferases (HDACs).
These specific enzymes catalyse the transfer of an acetyl group from
acetyl-CoA molecules to the lysine ɛ-amino groups on the N-terminal tails
of histones.
Acetylation of lysines neutralizes the charge on histones
therefore, increasing chromatin accessibility.
Following the discovery of histone acetylation, numerous studies have
shown that this type of modification occurs throughout the whole
eukaryotic genome.

8. METHYLATION
Methylation has been suggested to be biochemically stable and irreversible.
In other words, methylation could be a dead-end modification.
Once you have it, there is no way back.
The major methylation sites within histone tails are the basic amino acid side chains of lysine and arginine
residues).
Histone methyltransferases (HMTs) is the enzyme responsible for these modifications.
Several studies on bulk histones have indicated that mammals possess different ratios of methylated species of
lysine and arginine, depending on the cell type or tissue source.

9. In vivo, methylated lysines can be found
either in a mono-, di-, or trimethylated
state,
whereas arginines can be either mono- or
dimethylated (which can be asymmetric
or symmetric)
H3 methylation at Lys 9 has the
opposite effect and therefore is
found in regions where transcription
is repressed by chromatin structure

10. HISTONE
PHOSPHORYLATION
Histone phosphorylation involves the addition of phosphate
groups to the histone tail.
it is somewhat less well understood than are acetylation and
methylation.
Several nuclear protein kinases and protein phosphatases are
known to add or remove phosphate group to histones.

11. Histone phosphorylation is a critical intermediate step in chromosome condensation during cell division,
transcriptional regulation, and DNA damage repair.
Unlike acetylation and methylation, histone phosphorylation establishes interactions between other
histone modifications and serves as a platform for effector proteins, which leads to a downstream
cascade of events.
Phosphorylation occurs on all core histones, with differential effects on each.
Phosphorylation of histone H3 at serine 10 and 28, and histone H2A on T120, are involved in chromatin
compaction and the regulation of chromatin structure and function during mitosis. These are important
markers of cell cycle and cell growth that are conserved throughout eukaryotes.
Phosphorylation of H2AX at S139 (resulting in γH2AX) serves as a recruiting point for DNA damage repair
proteins and is one of the earliest events to occur after DNA double-strand breaks.