Epigenetic and genetics of Development Flashcards
week 11
Epigenetics
study of changes in phenotype or gene expression caused by mechanisms that do not involve changes in underlying DNA seq
How do embryonic cells become different if they are exact copes of a parent cell?
Differentiated cells arise from a sequence of increasingly specialized progenitor cells intermediates via epigenetic changes
How does chromatin change to euchromatin or heterochormatin?
epigenome controls the switching between these states.
what two mechanisms induce epigenetic change?
Histone modification
DNA methylation
How does Histone modification act as a mechanism for epigenetic change?
Sets a genes expression state (modifies activity of DNA wrapped around them)
Increased methylation of histone tail = repressed gene expression (promotes heterochromatin formation)
What is DNA methylation?
Covalent addition of a Me group at C5 of cytosine ( = 5-methylcytosine=5MEC)
What is a CpG island and how does it affect gene expression?
region of DNA containing high freq of CpG sites
methylation around gene promoters silence gene expression
How does DNA methylation repress transcription?
directly interferes with transcription factor binding, indirectly attracts specific repressor proteins.
Epigenetic Reprograming
Time during early embryonic development where all epigenetic tags are erased and remodelled.
Steps of epigenetic reprogramming
Parental epigenetic tags erased in formation of germ cells
Aprox 100 genes are reset. Their expression of allele depends on parent of origin.
Fertilization
Erasure of epigenetic tags so that all genes are available for embryonic development
As cell becomes more specialized, methylation increases.
What are imprinted genes?
genes that show expression of only maternal OR paternal allele
one copy is epigenetically silenced
is imprinting transmitted?
yes
Mitosis: epigenetic modifications are reproduced in new strands
Meiosis: imprints are removed and reset such that sperm is rewritten with paternak arks and oocytes rewritten with maternal marks.
Epigenetic traits vs trait caused by DNA mutation
Epigenetic traits DONT change the nucleotide seq but DO affect how genes behave.
Epigenetic trait = stable phenotype from change involving chemical modification of DNA bases or histone proteins
Mutations = change in DNA sequence
influence of diet in epigenome
Nutrient folic acid, VB and SAM-e are key components of methyl-making pathway
Diet high in these nutrient rapidly alter gene expression, especially during early development
intergenerational: transmission of epigenetic marks from one generation to another
Transgenerational: germ-line mediated inheritance of epigenetic information between generations in the absence of continued direct environmental influence. (not directly exposed).
Intergenerational: transmission of epigenetic marks from one generation to another
Transgenerational: germ-line mediated inheritance of epigenetic information between generations in the absence of continued direct environmental influence. (not directly exposed).
What ages are males and females sensitive to environmental exposure that leads to a transgenerational response?
Males: around age 10 when puberty begins with the production of sperm
Females: while still in the womb as eggs are being formed
what is the function of HOX genes?
Genes that direct formation of many body structures during early embryonic development
Controlled expression of a unique combination of homeobox genes = formation of each body segment
What is a complication of mutation in a HOX gene?
syndactyl
How is sex genetically determined?
SRY gene = transcription factor
SRY encodes TDF (Transcription factor protein)
TDF = HMG box that binds to DNA = initiates male sex determination and regulates male development.
What are regions of homology on each arm of the X and Y chromosome called?
pseudoautosomal regions (bind in meiosis)
How are XX males and XY females possible?
SRY is near telomere and PAR
Telomere region is prone to damage
Incorrect repair of this region = SRY being lost to X via crossing over
PAX6
Master control gene of ocular and neural tube development
11p13
What is Aniridia and what gene does it impact?
development of the eye but without an iris (aniridia) → cannot control light entering the eye
Pax6 gene 11p13
What is a critical period?
Time when organs are developing = emryois are most vulnerable to toxins, viruses and genetic abnormalities (due to elevated cell division during organogenesis)
Tetratogens
Agents that disrupt normal cellular development during embryogenesis = malformations and birth defects
3 categories of tetraogens
Drugs
Nutrients
Infection
What condition can arise from exposure to thalidomide
Phocomelia (seal limb) = total absence of long bones in limb
The difference in phenotype due to how early in the critical period of mother started it, for low long and dose
Describe the cause of willi prader syndrome
loss of paternal 15q11-13 region so only MATERNAl is remains, however these are switched off = disease
describe the cause of angleman disease
loss of maternal genes so only PATERNAL genes remains, however, these are switched off = disease
clincial features of willi prader syndrome
- chronic feeling of hunger → hyperphagia
- life-threatening obesity
compare Angleman And WP syndrome
both =methylation defect
AM= paternal uniprental disomy
WP = maternal uniparental disomy
epigenome
all chemical compounds that have been added to entire DNA as a way to regulate genes
methylome
set of nucleic acid methylation modification in genome or particular cell
Phocomelia clinical features
affects upper and lower limbs
-bones of affected limb missing/unaffected
-limb extremely short
-severe = hand/foot attaches to trunk
haploinsufficiency
only a single functional copy of a gene does not produce enough [product to produce wild-type = abnormal or disease state
What is the affect of histone acetylase on chromatin structure and gene trabscription
histone acetylase = increased histone acetylation = acetyl group is added = decreases the binding between histones and DNA = open structure (euchromatin)
