This document discusses epigenetic modifications of proteins. It begins by defining epigenetics and describing how epigenetic modifications can alter gene expression without changing DNA sequences. It then focuses on histone modifications like acetylation, methylation, ubiquitination, and phosphorylation. The document also examines epigenetic modifications of specific proteins - Sox2, CCAAT/enhancer binding protein a (C/EBPa), and caveolae associated proteins. It provides details on studies that analyzed the methylation of promoters for these genes in cancer cell lines and patient samples.
Dna methylation ppt
definition of Dna methylation ppt
discovery of Dna methylation ppt
types of Dna methylation ppt
history of Dna methylation ppt
process of Dna methylation ppt
mechanism of Dna methylation ppt
methylation in cancer
cytosine methylation
genomic imprinting
This presentation on Epigenetics is most advanced and evidence based one. Its Very helpful for Genetics students and research fellows, Reproductive Medicine specialist, Reproductive Biologist, Infertility practitioners
Epigenetics is the study, in the field of genetics, of cellular and physiological phenotypic trait variations that are caused by external or environmental factors that switch genes on and off and affect how cells read genes instead of being caused by changes in the DNA sequence. -Wikipedia
Dna methylation ppt
definition of Dna methylation ppt
discovery of Dna methylation ppt
types of Dna methylation ppt
history of Dna methylation ppt
process of Dna methylation ppt
mechanism of Dna methylation ppt
methylation in cancer
cytosine methylation
genomic imprinting
This presentation on Epigenetics is most advanced and evidence based one. Its Very helpful for Genetics students and research fellows, Reproductive Medicine specialist, Reproductive Biologist, Infertility practitioners
Epigenetics is the study, in the field of genetics, of cellular and physiological phenotypic trait variations that are caused by external or environmental factors that switch genes on and off and affect how cells read genes instead of being caused by changes in the DNA sequence. -Wikipedia
This presentation is about Genomic imprinting. Genomic imprinting is only found in eutherians. In next few slides we'll try to understand this phenomena.
Introduction
What RNA Splicing???
Discovery
Types
Alternative Splicing
Mechanism
Regulatory element And protein
Splicing repression
Splicing activation
Significance
Diseases
Conclusion
Refrences
"Epigenetics refers to genetic factors that change an organism’s appearance or biological functions without changing the actual DNA sequence. In other words, gene expression changes but the genes themselves don’t. Epigenetics adds an additional level of complexity to the genetic code." - Public Health Cafe
Alternative splicing is a deviation from the conventional splicing as it removes introns in a different manner. It has a lot of significance in the development of diseases like cancers and in plants adapting to various stress conditions.
This presentation is about Genomic imprinting. Genomic imprinting is only found in eutherians. In next few slides we'll try to understand this phenomena.
Introduction
What RNA Splicing???
Discovery
Types
Alternative Splicing
Mechanism
Regulatory element And protein
Splicing repression
Splicing activation
Significance
Diseases
Conclusion
Refrences
"Epigenetics refers to genetic factors that change an organism’s appearance or biological functions without changing the actual DNA sequence. In other words, gene expression changes but the genes themselves don’t. Epigenetics adds an additional level of complexity to the genetic code." - Public Health Cafe
Alternative splicing is a deviation from the conventional splicing as it removes introns in a different manner. It has a lot of significance in the development of diseases like cancers and in plants adapting to various stress conditions.
Cancer Epigenetics: Concepts, Challenges and PromisesMrinmoy Pal
The presentation highlights how recent investigations have shown extensive reprogramming of almost every component of the epigenetic machinery in cancer leading to the emergence of the promising field of epigenetic therapy.
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Presentation include Nucleus and its components like nuclear envelope, nucleolus, chromatin fibers, ultra structure of nucleus and its general functions.
Nutraceutical market, scope and growth: Herbal drug technologyLokesh Patil
As consumer awareness of health and wellness rises, the nutraceutical market—which includes goods like functional meals, drinks, and dietary supplements that provide health advantages beyond basic nutrition—is growing significantly. As healthcare expenses rise, the population ages, and people want natural and preventative health solutions more and more, this industry is increasing quickly. Further driving market expansion are product formulation innovations and the use of cutting-edge technology for customized nutrition. With its worldwide reach, the nutraceutical industry is expected to keep growing and provide significant chances for research and investment in a number of categories, including vitamins, minerals, probiotics, and herbal supplements.
Professional air quality monitoring systems provide immediate, on-site data for analysis, compliance, and decision-making.
Monitor common gases, weather parameters, particulates.
A brief information about the SCOP protein database used in bioinformatics.
The Structural Classification of Proteins (SCOP) database is a comprehensive and authoritative resource for the structural and evolutionary relationships of proteins. It provides a detailed and curated classification of protein structures, grouping them into families, superfamilies, and folds based on their structural and sequence similarities.
Earliest Galaxies in the JADES Origins Field: Luminosity Function and Cosmic ...Sérgio Sacani
We characterize the earliest galaxy population in the JADES Origins Field (JOF), the deepest
imaging field observed with JWST. We make use of the ancillary Hubble optical images (5 filters
spanning 0.4−0.9µm) and novel JWST images with 14 filters spanning 0.8−5µm, including 7 mediumband filters, and reaching total exposure times of up to 46 hours per filter. We combine all our data
at > 2.3µm to construct an ultradeep image, reaching as deep as ≈ 31.4 AB mag in the stack and
30.3-31.0 AB mag (5σ, r = 0.1” circular aperture) in individual filters. We measure photometric
redshifts and use robust selection criteria to identify a sample of eight galaxy candidates at redshifts
z = 11.5 − 15. These objects show compact half-light radii of R1/2 ∼ 50 − 200pc, stellar masses of
M⋆ ∼ 107−108M⊙, and star-formation rates of SFR ∼ 0.1−1 M⊙ yr−1
. Our search finds no candidates
at 15 < z < 20, placing upper limits at these redshifts. We develop a forward modeling approach to
infer the properties of the evolving luminosity function without binning in redshift or luminosity that
marginalizes over the photometric redshift uncertainty of our candidate galaxies and incorporates the
impact of non-detections. We find a z = 12 luminosity function in good agreement with prior results,
and that the luminosity function normalization and UV luminosity density decline by a factor of ∼ 2.5
from z = 12 to z = 14. We discuss the possible implications of our results in the context of theoretical
models for evolution of the dark matter halo mass function.
This pdf is about the Schizophrenia.
For more details visit on YouTube; @SELF-EXPLANATORY;
https://www.youtube.com/channel/UCAiarMZDNhe1A3Rnpr_WkzA/videos
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What is greenhouse gasses and how many gasses are there to affect the Earth.moosaasad1975
What are greenhouse gasses how they affect the earth and its environment what is the future of the environment and earth how the weather and the climate effects.
Cancer cell metabolism: special Reference to Lactate PathwayAADYARAJPANDEY1
Normal Cell Metabolism:
Cellular respiration describes the series of steps that cells use to break down sugar and other chemicals to get the energy we need to function.
Energy is stored in the bonds of glucose and when glucose is broken down, much of that energy is released.
Cell utilize energy in the form of ATP.
The first step of respiration is called glycolysis. In a series of steps, glycolysis breaks glucose into two smaller molecules - a chemical called pyruvate. A small amount of ATP is formed during this process.
Most healthy cells continue the breakdown in a second process, called the Kreb's cycle. The Kreb's cycle allows cells to “burn” the pyruvates made in glycolysis to get more ATP.
The last step in the breakdown of glucose is called oxidative phosphorylation (Ox-Phos).
It takes place in specialized cell structures called mitochondria. This process produces a large amount of ATP. Importantly, cells need oxygen to complete oxidative phosphorylation.
If a cell completes only glycolysis, only 2 molecules of ATP are made per glucose. However, if the cell completes the entire respiration process (glycolysis - Kreb's - oxidative phosphorylation), about 36 molecules of ATP are created, giving it much more energy to use.
IN CANCER CELL:
Unlike healthy cells that "burn" the entire molecule of sugar to capture a large amount of energy as ATP, cancer cells are wasteful.
Cancer cells only partially break down sugar molecules. They overuse the first step of respiration, glycolysis. They frequently do not complete the second step, oxidative phosphorylation.
This results in only 2 molecules of ATP per each glucose molecule instead of the 36 or so ATPs healthy cells gain. As a result, cancer cells need to use a lot more sugar molecules to get enough energy to survive.
Unlike healthy cells that "burn" the entire molecule of sugar to capture a large amount of energy as ATP, cancer cells are wasteful.
Cancer cells only partially break down sugar molecules. They overuse the first step of respiration, glycolysis. They frequently do not complete the second step, oxidative phosphorylation.
This results in only 2 molecules of ATP per each glucose molecule instead of the 36 or so ATPs healthy cells gain. As a result, cancer cells need to use a lot more sugar molecules to get enough energy to survive.
introduction to WARBERG PHENOMENA:
WARBURG EFFECT Usually, cancer cells are highly glycolytic (glucose addiction) and take up more glucose than do normal cells from outside.
Otto Heinrich Warburg (; 8 October 1883 – 1 August 1970) In 1931 was awarded the Nobel Prize in Physiology for his "discovery of the nature and mode of action of the respiratory enzyme.
WARNBURG EFFECT : cancer cells under aerobic (well-oxygenated) conditions to metabolize glucose to lactate (aerobic glycolysis) is known as the Warburg effect. Warburg made the observation that tumor slices consume glucose and secrete lactate at a higher rate than normal tissues.
Introduction:
RNA interference (RNAi) or Post-Transcriptional Gene Silencing (PTGS) is an important biological process for modulating eukaryotic gene expression.
It is highly conserved process of posttranscriptional gene silencing by which double stranded RNA (dsRNA) causes sequence-specific degradation of mRNA sequences.
dsRNA-induced gene silencing (RNAi) is reported in a wide range of eukaryotes ranging from worms, insects, mammals and plants.
This process mediates resistance to both endogenous parasitic and exogenous pathogenic nucleic acids, and regulates the expression of protein-coding genes.
What are small ncRNAs?
micro RNA (miRNA)
short interfering RNA (siRNA)
Properties of small non-coding RNA:
Involved in silencing mRNA transcripts.
Called “small” because they are usually only about 21-24 nucleotides long.
Synthesized by first cutting up longer precursor sequences (like the 61nt one that Lee discovered).
Silence an mRNA by base pairing with some sequence on the mRNA.
Discovery of siRNA?
The first small RNA:
In 1993 Rosalind Lee (Victor Ambros lab) was studying a non- coding gene in C. elegans, lin-4, that was involved in silencing of another gene, lin-14, at the appropriate time in the
development of the worm C. elegans.
Two small transcripts of lin-4 (22nt and 61nt) were found to be complementary to a sequence in the 3' UTR of lin-14.
Because lin-4 encoded no protein, she deduced that it must be these transcripts that are causing the silencing by RNA-RNA interactions.
Types of RNAi ( non coding RNA)
MiRNA
Length (23-25 nt)
Trans acting
Binds with target MRNA in mismatch
Translation inhibition
Si RNA
Length 21 nt.
Cis acting
Bind with target Mrna in perfect complementary sequence
Piwi-RNA
Length ; 25 to 36 nt.
Expressed in Germ Cells
Regulates trnasposomes activity
MECHANISM OF RNAI:
First the double-stranded RNA teams up with a protein complex named Dicer, which cuts the long RNA into short pieces.
Then another protein complex called RISC (RNA-induced silencing complex) discards one of the two RNA strands.
The RISC-docked, single-stranded RNA then pairs with the homologous mRNA and destroys it.
THE RISC COMPLEX:
RISC is large(>500kD) RNA multi- protein Binding complex which triggers MRNA degradation in response to MRNA
Unwinding of double stranded Si RNA by ATP independent Helicase
Active component of RISC is Ago proteins( ENDONUCLEASE) which cleave target MRNA.
DICER: endonuclease (RNase Family III)
Argonaute: Central Component of the RNA-Induced Silencing Complex (RISC)
One strand of the dsRNA produced by Dicer is retained in the RISC complex in association with Argonaute
ARGONAUTE PROTEIN :
1.PAZ(PIWI/Argonaute/ Zwille)- Recognition of target MRNA
2.PIWI (p-element induced wimpy Testis)- breaks Phosphodiester bond of mRNA.)RNAse H activity.
MiRNA:
The Double-stranded RNAs are naturally produced in eukaryotic cells during development, and they have a key role in regulating gene expression .
Multi-source connectivity as the driver of solar wind variability in the heli...Sérgio Sacani
The ambient solar wind that flls the heliosphere originates from multiple
sources in the solar corona and is highly structured. It is often described
as high-speed, relatively homogeneous, plasma streams from coronal
holes and slow-speed, highly variable, streams whose source regions are
under debate. A key goal of ESA/NASA’s Solar Orbiter mission is to identify
solar wind sources and understand what drives the complexity seen in the
heliosphere. By combining magnetic feld modelling and spectroscopic
techniques with high-resolution observations and measurements, we show
that the solar wind variability detected in situ by Solar Orbiter in March
2022 is driven by spatio-temporal changes in the magnetic connectivity to
multiple sources in the solar atmosphere. The magnetic feld footpoints
connected to the spacecraft moved from the boundaries of a coronal hole
to one active region (12961) and then across to another region (12957). This
is refected in the in situ measurements, which show the transition from fast
to highly Alfvénic then to slow solar wind that is disrupted by the arrival of
a coronal mass ejection. Our results describe solar wind variability at 0.5 au
but are applicable to near-Earth observatories.
2. OUTLINE
What is epigenetics?
Epigenetic Modification of Histone
Proteins
Epigenetic Modifications of
Sox 2
CCAAT/enhancer binding protein a (C/EBPa)
Caveolae associated proteins
3. Epigenetics
- Literally means "above" or "on top of" genetics.
- ‘Heritable changes in gene activity and expression that
occur without alteration in DNA sequences’
- i.e. a change in phenotype without a change in genotype.
- Epigenetics is the reason why a skin cell looks different
from a brain cell or a muscle cell. All three cells contain the
same DNA, but their genes are expressed differently
(turned "on" or "off"), which creates the different cell types.
4. Can be achieved by…..
1) DNA methylations
2) Histone Modifications
3) Post translational Modifications
5. Modifications of Histones
- Histones are highly alkaline proteins found in eukaryotic
cell nuclei that package and order the DNA into structural
units called nucleosomes.
7. 1) Histone Acetylation and deacetylation:
• a highly dynamic process that is regulated by two
families of enzymes — histone acetyltransferases (HATs)
and HDACs
• HATs use acetyl-CoA as a cofactor and catalyze the
transfer of an acetyl group to the ε-amino group of lysine
side chains on the histone protein. This neutralizes the
positive charge on lysine, thus reducing the affinity of the
histone tail that protrudes from the nucleosome core of
DNA. As a result, chromatin adopts a more relaxed
structure, enabling the recruitment of the transcriptional
machinery.
• HDACs reverse the acetylation of lysine residues to restore
their positive charge and stabilize the local chromatin
architecture.
8. 2) Histone Methylation:
• Lysine residues on histones can be monomethylated,
dimethylated or trimethylated.
• Arginine residues are also subject to monomethylation
and dimethylation.
• Methyl marks are written by S-adenosylmethionine (SAM)-
dependent methyltransferases and erased by the Jumonji
family of 2-oxoglutarate-dependent demethylases.
• Histone lysine methylation can be associated with either
transcriptional activation (H3K4me3) or repression
(H3K9me3 and H3K27me3 )
9. 1) Sox 2
• SRY (sex determining region Y)-box 2, also known as SOX2, is
a transcription factor that is essential for maintaining self-
renewal, or pluripotency, of undifferentiated embryonic stem
cells.
• Sox2, a critical transcription regulator of embryonic and neural
normal stem cell function, has been reported to be dysregulated
in several human cancers.
• Sox2 was found to be frequently downregulated in gastric
cancers and overexpressed in small-cell lung cancers,
esophageal squamous carcinomas, and basal cell-like breast
carcinomas.
• Sox2 locus was shown to be amplified in small-cell lung cancer,
esophageal squamous carcinomas and, to a lesser extent, in
GBM .
• Sox2 promoter hypomethylated in Sox2-expressing cell lines
and Sox2- negative cell lines exhibited a methylated promoter
pattern ( Marta,Ricardo et al. 2011)
10. Epigenetic Modification of Sox 2
• The glioma cell lines LN229, U87 MG, U251 MG, U373, A172,
SNB19, D54 and human GBM surgical specimens.
1) Sox2 Expression Levels by Quantitative PCR.
2) Assessment of SOX2 Promoter Methylation:
- DNA was extracted from cell lines and patients.
11. - analyzed SOX2 promoter methylation using MSP primer pairs.
Results:
1) Sox 2 Expression levels:
2) Assessment of SOX2 Promoter Methylation
12. 2) CCAAT/Enhancer Binding Protein A
• CCAAT/enhancer binding protein a (C/EBPa), is a key
transcription factor involved in the regulation of cell
proliferation and differentiation in a variety of cell
types, particularly in the hematopoietic system.
• Under physiologic conditions, C/EBPa is a master
regulator for myeloid differentiation and granulocytic
maturation, its absence results in a block of
granulopoiesis.
• Aberrant promoter methylation of C/EBPa is a
common event in AML.( Kristi, Romulo 2008)
13. Epigenetic Modification of C/EBPa
- One hundred forty-six bone marrow samples from AML patients.
- DNA and RNA Isolation.
- Assessment of C/EBPa methylation by COBRA.
[Combined Bisulfite Restriction Analysis (or COBRA) is a molecular
biology technique that allows for the sensitive quantification of DNA
methylation levels at a specific genomic locus on a DNA sequence in a
small sample of genomic DNA. The technique is a variation of bisulfite
sequencing, and combines bisulfite conversion based polymerase chain
reaction with restriction digestion. ]
14. Results:
-Aberrant DNA methylation in the upstream promoter of C/EBPa is a
frequent event in AML.
- A distinct pattern of aberrant DNA methylation in region 1 was seen in
51% of AML patient samples, whereas the core promoter and all other
investigated regions remained unmethylated.
15. 3) caveolae associated proteins
• small specialized “cave-like” microdomains at the plasma membrane
that function as trafficking vesicles and are involved in organization
of signal transduction.
• Caveolae are present in most tissues and are particularly abundant in
cardiac, continuous endothelial and epithelial cells.
• Within caveolae are caveolae associated proteins;
1) caveolin-1 (CAV1)
2) caveolin-2 (CAV2) ,
3) caveolin-3 (CAV3),
• Cavin-1 (also know as polymerase-1 and transcript release factor)
(PTRF) ,
• Cavin-2 , Cavin-3 and Cavin-4 , which are important for the
formation and maintenance of the caveolar structure..
16. CAV 1 Protein
• CAV1 is a 22 kDa protein which is the principal substrate
of src kinase and appears as a filament-like structure at the
plasma membrane .
• CAV1 is expressed in a wide range of tissues with the
highest expression in smooth muscle cells, adipocytes,
fibroblasts and endothelial cells.
• CAV1 plays an important role in the formation of caveolae;
if cells lack CAV1, no caveolae are observed.
Epigenetic Modifications of CAV 1
• The 5′ promoter of CAV1 is methylated in human breast cancer
cell lines MDA-MB-231, MCF7 and T-47D but not in normal human
mammary epithelial cells.
• Studies of clinical tissues have shown that breast cancer tissues have
hypermethylation of the CAV1 promoter.
17. • Because of hypermethylation of CAV 1 promoter , there is
down-regulation of CAV1 expression when compared to
adjacent normal breast tissues.
• In prostate cancer, CAV1 is down-regulated and this is
accompanied by promoter hypermethylation of CpGi sites
at the 5′ promoter region of CAV1.
• Treatment with 5-AZA has been shown to restore CAV1
expression in some cancers confirming hypermethylation.
18. REFERNCES
1. Bjo¨rn Hackanson, Kristi L. Bennett, Epigenetic Modification of
CCAAT/Enhancer Binding Protein A Expression in Acute
Myeloid Leukemia, Cancer Res 2008; 68: (9).
2. Cheryl H. Arrowsmith, Chas Bountra, Epigenetic protein families :
a new frontier for drug discovery, Nature Reviews, (MAY 2012)
VOLUME 11, 384-400
3. Jin-Yih Low and Helen D. Nicholson, Epigenetic modifications of
caveolae associated proteins in health and disease, Low and
Nicholson BMC Genetics (2015) VOL 16:71.
4. Marta M. Alonso1, Ricardo Diez-Valle, Genetic and Epigenetic
Modifications of Sox2 Contribute to the Invasive Phenotype of
Malignant Glioma, PLoS ONE, (November 2011), Volume 6 (11).