besic understand epigenetics

1. EPIGENETICS
Presented by
DIBYA RANJAN NATH

2. Epigenetics at a glance
• It is a modern branch of genetics which
providing us with a basis for elucidating how
heritable changes other than those in DNA
sequence can influence phenotypic variation.
• Epigenetic gene regulation use reversible
modification of DNA &chromatin structure to
mediate interaction of the genome with a varity
of environmental factor & to generate change
pattern of gene expression in response to those
factor .

3. • Change may be transcription level or mRNA
level.
• Modified into different genome to become
complex & each modified genome called
epigenome.
• Epigenetic trait is stable both mitotically &
meotically heritable phenotype that capable to
change gene expression.
• Due to epigenetic modification different
diseases occur like dibetics,asthma&cancer etc.

4. What is intracellular signal to induce
epigenome?
• Cellular response pathway in epigenetics
organized three categories of change.
• 1.epigenetor(carcinogen,uv radiation &
environmental stress etc).
• 2.epigenetic initiators;-it includes protein
signal transduction pathway,DNA binding
protein,non coding RNA(siRNA).
• 3.epigenetic maintainers;-these are not
sequence specific in molecular level after
modification maintained by
DNAmethylase,DNAacetylase&deacetylase.

6. Histone modification
• It is an important epigenetic mechanism of
gene regulation .
• Amino acid in N-terminal region of histone can
be covalently modified in several ways includes
acetylation ,phosphorylation,methylation.
• Normally histones are modified by acetylation
by histoneacetyl transferase(HAT) open for
transcription and deacetylase (HDAC) changing
the chromatin closed and silenced the gene
making unfevorable for transcription.

8. Cntd..
• Other events also includes presence or absence
of methyl group on histones.
• Methylation in lysine4/27 in H3 causes
transcriptional activation while in lysine9
causes transcriptional silencing.
• Phosphorylation also occur if serine10
phosphorylation lysine9 methylation inhibited
if lysine14 deacetylated methylation of lysine9
is facilited.
• This pattern and interaction histone
modification called histone code

9. RNA interference
• During epigenetic regulation small noncoding
RNA(siRNA) participate in methylation
&histone modification .
• siRNA associate with protein to form RNA-
induced silencing complex(RISC).
• If siRNA perfectly complementary to mRNA
then it will cleave mRNA and destroyed then
gene silencing effectively occur .
• It acts directly preventing trancription factor
binding at initiation of transcription
TFiiB&RNA polymerase.

10. Cntd..
• Another process short RNA molecule can also
associate with protein complex to form RNA
induced transcriptional silent(RITS) complex
&induce formation of facultative
heterochromatin that silent gene.

11. Different non-coding RNA role in
Epigenetics
• miRNA-Micro RNA regulate gene expression by
blocking translation of specific mRNAs and cause
their degradation.
siRNA-Turn off gene regulation by directing
degradation of selective mRNA.
• piRNA-Bind piwi proteins &protect the germ line
from transposable element.
• lncRNA-long non-coding RNA many which
serves as scaffolds ,including X-chromosome
inactivation.

12. Environment impact &epigenome
• Different environment agents like
nutrient,chemicals &physical factors has
effect on epigenetic changes.
• In human it is very difficult to determine the
change in epigenome due to environmental
&learned behavior but has evidence mainly
that agents affect the endocrine system.
• For example:- mice coat colour(aghouti
&yellow) change due to affect allele.

13. Cntd..
• A drug(dietyl still bestol) used in USA several
decade for prevent complication of pregnancy
and miscarriage.
• It would increase high risk of vaginal &breast
cancer (female),in male it also affect in
neurological and behavioral alteration.

14. Epigenetic modification affect
behavior
• Epigenetic changes include alteration
methylation pattern and histone modification
may be important component in behavioral
change.
• Best example in case of honey bee worker.
• Worker and queen have same genome worker
is sterile but queen fertile .
• That epigenetic change occur by royal jelly ,it
was discovered by Ryszard Kucharski and
colleague in 2008.

15. Cntd..
• Royal jelly silence a key gene called Dnmt3
whose product add normally methyl group to
DNA with Dnmt3 silencing beeDNA is less
methylated that stimulate queen devlopment.
• In case human also seen that epigenetic changes
in case of neurodegenerative disorders
&neuropsychiatric with alter behavioural
phenotype.

16. Modification due to genome
imprinting
• Phenomenon of the differential expression of
genetic material depending either it is inherited
from male or female parents called genome
imprinting.
• Due to genome imprinting Mendels reciprocal
cross do not give identical result.
• Due to genome imprinting one Xchromosome
remain inactive and expression is balanced.
• During gamete formation differential CpG
methylation occur which helps in allele specific
imprinting & subsequent gene silencing.

17. Cntd..
• Different evolutionary point of view different
maternal& paternal gene affect in fetal growth
(gene conflict hypothesis).
• Best example fetal development of human both
maternal & paternal IGF2 gene have capable
to grow fetus but fetus use paternal IGF2 for
best growth.
• In maternal case H19 gene expressed and IGF2
gene blocked by CTCF(transcriptional
repressor protein)

19. Epigenetics and cancer
• The relationship between cancer and Epigenetics was
first noted in 1980 by Feinberg and Vogelsten who
observed in colon cancer cell much lower level of
methylation than normal cells derived from same tissue.
• Studied that global hypermethylation(CpG) is property
of all cancer cell to date that selective
hypermethylation& gene silencing.
• DNA hypomethylation reverses the inactivation of
gene,leading to unrestricted transcription of many gene
sets including oncogene&mutation in histone modifying
gene seen in some case means dysfunctional
HAT&HDAC(Rubenstein-taybi syndrome).

20. Cntd..
• Hypomethylation of repetitive sequence leads
to transcriptional activation transposable DNA
sequences such as LINES(long interspersed
nuclear elements) & SINES further increase
genomic instability.
• Hypermethylation(CpG island) occur that silent
tumor supressing gene studied in some cancer
case.
• Now a day epigenetic therapy also use instead
of chemotherapy to express the silent gene.

21. Cntd..

22. How mutation differ from
Epigenetics
• Mutation directly affects DNA sequence and
occur permanent change but in epigenetic
changes temporary time period due to
different physical, chemical factors.
• In epigenetic changes recovered at time of
gamete formation but not in mutation.
• Epigenetics is reversible process but
mutation is irreversible process.

23. THANK YOU