Lecture 2 Flashcards
No change in actual structure of the gene, no nucleotide change… change in chromatin structure which turns gene off or on… chromatin change acures in germ cells
epigenetics inheritence
a form of inheritance that is superimposed on the genetic inhertance based on DNA
epigenetics
DNA sequnce changes
genetic inheritence
high degree of conservation in a structure indicates
high degree of importance
one form of chromatin silences the genes it packages without regard to sequence and is directly inherited by daughter cells
heterochromatin
heterochromatin
- heavily conserved
- thought to be late replicating and genetically inactive
- highly conserved at centromeres and telomeres
- contains very few genes; resistant to gene expression
- all the rest is less condensed and known as euchromatin
activity a gene depends on position on chromosome… will be silenced if relocated near heterochromatin
position effect.
breakage events that bring heterochromatin near active genes tends to silence them
position effect variegation…. zone of inactivation spreads a different distance in different cells
Histone modification
histone modification- loosens chromatin sturcutre
Acetylation of lysines… added by histone acetyl transferases (HATs); removed by histone deacetylase complexes (HDACs)
Histone modifications of serines
phosphorlation
What does recruitment of enzymes that cause histone modification depend on?
gene regulatory proteins
Are histone modifications reversible?
All are reversible, but can persist long after regulatory protieins have disappeared
What is important consequences for the types of proteins the modified DNA attract?
This determines the how when if gene expression takes place
What histone hast no variant histones?
H4
synthesized during S phase and assembled into nucleosomes on duaghter DNA helices just behind replication fork
major histones
synthesized during interphase and inserted into already formed chromatin. requires histone exchange process catalyzed by chromatin remodeling complex
variant histones
Histone code
thouseand of combinations of modifications (methylation, acetylation, etc)… ready by code reader complex
What binds and attracts other components??
code reader complex.. brings onther protein compexes
gene regulatory proteins has a histone modyfing enzyme “ writer”, the code-reader protein tells the other DNA about the change
code reader-writer
IS the chromatin remodeling comlex ATP dependent?
Yes,
How is remodeling contained to one area of the chromosome?
physical barriers… nuclear 4 complex, code reader complexes cannot go through
enzymatic barriers- HS4 region- protects the Beta globin locus from silencing, contains a cluster of histone actylase binding sites prevening writers from continuing
centromeric heterochromatin
centromere specific H3 histon, CENP-A, pack the nucleosoomes into dense arrangements to for the kinetochore
What does centromere sequences in humans consist of?
short repetitive DNA sequences called alpha satellite DNA
What is centromerica heterochromatin defined by?
assembly of proteins, not DNA sequences
alpha satellite DNA
at most centromeres, but not all. and at some areas that are not contromeres, the proteins that form to create the centromere is the MOST important aspect of centromere formation
What are 2 altering types of chromatin
nucelosomes w CENP-A on the outside fold
Nucleosomes w normal H3 on the inside
What does CENP-A do?
binds the kinetochore
What does de novo centromere formation require?
a “seeding” event on alpha satellite DNA
How are H3-H4 tetramers inherited?
Directly inherited by the daughter strands at the replication fork
Centromeres are not randomly placed on
chromosomes
structure of interphase chromosomes
extended loops to be more accesible
What is assocated with nuclear lamina?
heterochromatin
Each chromsomes occupies
its own areas of the nucleus, not each pair is next to one another
Chromatin structure and location chagnes during
gene expression
If a gene is being expressed it goes to?
a chromosomes loop
decondensation of chromatin during gene transcription;
chromosomes puffs
interior of nucleus very
hertogeneous
mitotic chromosomes are
highly condensed, final levle in chromosome packaging
two daughter DNA molecules replicated in interphase are speartely folded to produce
two sister chromatids
What are chromatids held together at?
chromatids
What is the purpose of consensation
protection of fragile DNA molecules
allow for separation for cell division
Compaction aided by proteins called
condensisns
genes that are similar in both sequence and fucntion due to common ancestry***
homologues… not the same as syntany
What is a major clue to gene and prtein function?
recognition of sequnce similarity
gene sequences are more tightly conserved than…
genome structure…. size of genome, number of genes, size of introns, abundance of repetitive sequences can be quite different
How do genomic changes occur??
mistakes in DNA replication and repair… rare in genetic material
types of genetic changes
base pair substitutions…
more lg scale=
duplications, deletions, inversinos, translocations
elimination of mutations that interfere with improant genetic functions
purifying selection
a duplicated gene that has become irreversibly inactivated by multiple mutations
pseudogenes
globin genes… duplication and divergence
intially there was one hemoglobin genes and now it has four.
SNPs. single-nucleotide
points in the gneome where one group has one nucleotide and another group as another
variation occurs at a high rate (1% or more)
CNVs- copy number variants
presence of many duplications and deletions of lg blocks of DNA
some blocks are common and others rare
