DIET AND THE EPIGENOME Flashcards
EPIGENETICS NAME MEANING?
‘EPI’ - GREEK; OVER, ABOVE
MEANING: ‘ON TOP OF GENETICS’
MAIN EPIGEN. MECHANISMS:
DNA METHYLATION, HISTONE MODIFICATIONS, NON-CODING RNA
WHAT ARE EPIGENETIC FACTORS?
EPIGEN FACTORS CAUSING HERITABLE CHANGE IN GENE EXPRESSION WITHOUT ALTERING DNA SEQUENCE
WHAT ARE SENSITIVE WINDOWS IN EPIGENETICS?
PERIODS IN WHICH OUR EPIGENOME IS AT ITS HIGHEST VULNERABILITY TO INTRINSIC AND EXTRINSIC FACTORS
THE EPIGENOME IS INFLUENCED AND DETERMINED BY 3 TYPES OF SIGNALS:
- EXTRINSIC ENVIRONMENTAL FACTORS (DIET, EXERCISE, DRUGS)
- INTRINSIC FACTORS (EPIGEN. PROGRAMMING, REPAIR MACHINERY…); THESE ARE ALSO SUSCEPTIBLE TO CHNAGE BY EXTRINSIC FACTORS
- INHERITED EPIGEN. MARKS (BEYOND ONE’S CONTROL, INCLUDE IMPRINTED GENES AND TRANSGENERATIONAL EPIGEN.=
REPROGRAMMING OF DNA METHYLATION DURING DEVELOPMENT OCCURS IN HOW MANY WAVES?
2
IN WHICH TRIMESTER DOES THE 1ST WAVE OF DNA METHYLATION REPROGRAMMING OCCUR?
1ST
1ST WAVE LOSS OF METHYLATION IN THE GENOME INHERITED FROM WHICH PARENT HAPPENS FASTER?
THE FATHER
AT WHICH STAGE DOES THE ZYGOTE REACH THE LOWEST LEVEL OF GLOBAL AND GENOME WIDE METHYLATION?
IS THIS BEFORE AND AFTER IMPLANTATION?
BLASTULA STAGE
PRE IMPLANTATION
WHEN DOES THE METHYLATION PATTERN REMOVED FROM THE ZYGOTE START REESTABLISHING?
AFTER IMPLANTATION
WHERE DOES THE 2ND WAVE OF REPROGRAMMING OF DNA METHYLATION OCCUR?
IN THE GERM CELLS OF THE DEVELOPING EMBRYO; PRIMORDIAL GERM CELLS (PGCs)
IN WHICH WAVE OF DNA METHYLATION REPROGRAMMING ARE THE IMPRINTING GENES RESET?
ONLY IN THE 2ND WAVE
DIETARY METHYL DONORS WHICH HELP ESTABLISH FETUS’ METHYLATION PATTERN WHEN THE MOTHER CONSUMES THEM THROUGH HER DIET?
METHIONINE, FOLATE, CHOLINE, VIT B12 (COBALAMIN)
WHICH VITAMIN IS A CO FACTOR FOR METHYLATION?
B12
WHERE IN THE HUMAN BODY IS VIT B12 SYNTHESISED BUT IT CAN’T BE TAKEN UP FROM THERE SO WE NEED TO ACQUIRE IT THROUGH DIET?
BY THE BACTERIA IN THE COLON
WHAT IS DIRECT EPIGENETIC MEMORY?
IT COMPRISES ALL OF THE EPIGENETIC CHANGES THAT OCCUR DURING AN INDIVIDUAL’S LIFESPAN AS A RESULT OF DIRECT EXPOSURE TO ENVIRONMENTAL FACTORS
WHAT DOES ‘EVENT FREE’ REFER TO IN EPIGENETICS?
COMPRISES ALL OF THE EPIGEN CHANGES THAT OCCUR DURING AN INDIVIDUALS LIFESPAN AS A RESULT OF AN EXPOSURE THAT OCCURRED OUTSIDE THE INDIVIDUAL’S LIFETIME
MULTIGENERATIONAL EXPOSURE IN EPIGENETICS REFERS TO?
MORE THAN ONE GENERATION BEING DIRECTLY EXPOSED TO TO THE EVENT
WHAT DOES EPIGENETIC INHERITANCE REFER TO?
THE TRANSMISSION OF CERTAIN EPIGENETIC MARKS TO OFFSPRING
WHAT ARE INTERGENERATIONAL EPIGENETIC EFFECTS?
THEY OCCUR WHEN MATERNAL ENVIRONMENTAL EXPOSURES HAVE DIRECT EFFECTS ON THE GERM CELLS OR DEVELOPING FETUS LEADING TO ALTERED PHENOTYPE OF THE CHILD AND POSSIBLY GRANDCHILD
WHAT ARE TRANSGENERATIONAL EPIGENETIC EFFECTS?
WHEN EPIGEN. CHANGES ARE TRANSMITTED TO THE F2 ON THE PATERNAL LINE OR F3 ON THE MATERNAL LINE WHEN EXPOSURE OCCURS DURING PREGNANCY IN THE ABSENCE OF FURTHER ENVIRONMENTAL EXPOSURE
DIETHYLSTILBESTROL (DES) WAS USED IN 1950S FOR WHAT PURPOSES?
WHY ISN’T IT USED IN THE SAME WAY ANY MORE?
WHAT IS IT USED FOR NOW?
- WAS USED TO PREVENT SPONTANEOUS ABORTIONS
- CAUSED INCREASED BREAST AND TESTICULAR CANCER IN ADULT OFFSPRING
- NOW USED AS HORMONAL THERAPY TO TREAT PROSTATE CANCER
FETAL PROGRAMMING OF ADULT DISEASE IS ALSO KNOW AS?
DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE
HOW MANY CpG ISLANDS (LOCATIONS THAT CAN BE METHYLATED) DOES POMC GENE (HAS A ROLE IN HYPOTHALAMUS FOR DECREASING FOOD INTAKE) HAVE?
2
HOW CAN STRESS AND NUTRITION INFLUENCE METHYLATION IN POMC GENE AND WHAT IS THE RESULT OF THIS?
THEY CAN INDUCE METHYLATION WHICH LEADS TO REDUCED ACTIVITY IN THE GENE MEANING APPETITE IS LESS CONTROLLED WHICH CAN LEAD TO INCREASED LIPIDS AND OBESITY
WHAT IS ONE CARBON METABOLISM?
Encompasses both the folate and methionine cycles and allows cells to generate one-carbon units (also referred to as methyl groups) and utilise them for the biosynthesis of important anabolic precursors and for methylation reactions
WHICH TWO CYCLES COMPRISE ONE CARBON METABOLISM?
METHIONINE AND FOLATE
3 TYPES OF MOUSE BASED ON EXPRESSION OF AGOUTI SIGNALLING PROTEIN (FROM AGOUTI GENE)
WILD TYPE: AGOUTI GENE METHYLATED, FUR BLACK/BROWN WITH YELLOW BANDS FROM TRANSIENTLY EXPRESSED GENE (AGOUTI mRNA BRIEFLY MADE DURING DEVELOPMENT AND THEN SILENCED FOR THE REST OF MOUSE’S LIFE)
VIABLE AGOUTI MOUSE: LACK OF METHYLATION OF THE AGOUTI GENE SO IT STAYS CONTINUOUSLY ACTIVE AND EVEN EXPRESSED IN OTHER TISSUES (LIKE HYPOTHALAMUS); THE MOUSE’S FUR IS FULLY YELLOW AND IT WILL DEVELOP OBESITY AND DIABETES LATER IN LIFE
PSEUDO-AGOUTI MOUSE; AGOUTI GENE ITSELF ISN’T METHYLATED BUT INTRACISTERNAL A PARTICLE (IAP, ONE OF THE MOST REACTIVE RETROTRANSPOSONS IN THE MOUSE GENOME) IS INSERTED BEFORE THE GENE AND METHYLATED, SUPRESSING THE GENE EXPRESSION, SO THE MOUSE LOOKS LIKE THE WILD TYPE; THE LEVEL OF METHYLATION IN IAP CpG SITE CAN VARY IN DIFFERENT CELLS SO THE EXPRESSION OF AGOUTI GENE CAN VARY IN PATCHES OF CELLS (MOSAICISM) LEADING TO A SPECTRUM OF PHENOTHYPES
