Chapter 11 Flashcards
how do differences in anatomy, physiology and behavior between cells appear?
those cells are all derived from the same genetic material
> those differences are due to different patterns of gene expression
which RNA polymerase transcribes all protein coding genes?
RNA polymerase 2
which RNA polymerase is responsible for mtDNA?
mitochondria have entirely different RNA polymerase, encoded by the nuclear “POLRMT” gene
which elements have to be present in the genetic code to start transcription?
but?
- BRE - TF2B recognitin element
- TATA-box - recognized by TBP subunit
- Inr - initiator elements, 25-30 bp further than TATA box
> contains transcription start site
- DPE - downstream core promotor element
BUT none of these elements is either necessary or sufficient
what is a major difference between RNA and DNA polymerase?
RNA polymerase does not need a primer to get started
how is RNA transcription terminated?
RNA transcription terminated
> no specific signal in sequence
> protein complex cuts transccript and exonuclease moves along RNA until it reaches polymerase > transcript ends
which transcription factor binds first?
how does it recognize the TATA box?
transcriptionfactor TFIID binds first
> one subunit of this factor is called TBP, which recognizes the TATA box
how is transcription regulated by enhancers and activators?
transcription regulation
> activators bind to enhancers (or repressors bind to silencers)
> activators bind to transcription factors
> binding of activators stimulates transcription initiation
what are locus of control regions?
LCR’s
> stimulate the expression on genes
> contain DNase1 hypersensitivity sites, positions where nucleosomes are modified or absent: proteins can bind
> these binding proteins control the chromatin structure
where are enhancers or silencers located?
how are direct interactions with the promoter possible?
enhancers or silencers can be located hundreds of kilobases up or downstream from the gene they control
> DNA looping enables physical interaction between proteins bound to enhancers/silencers and RNA polymerase attached to promoter
what is the definition of epigenetics?
epigenetics
heritable changes in gene expression that do not involve changes to the underlying DNA sequence
> a change in phenotype without a change in genotype
by what factors can epigenetics be influenced?
epigenetic chance is a regular and natural occurrence but can also be influenced by several factors including age, environment,lifestyle and disease state
what are the two main components of epigenetic code?
epigenetic code mainly consists of
- DNA methylation
> methyl marks added to certain DNA bases repress gene activity
- histone modification
> different molecules can attach to the histone tails and alter the activity of the DNA wrapped around them
where can DNA methylation occur?
> how are those sites called?
> by which enzyme?
the 5’ position of a cytosine base can be methylated
> but only cytosines whose downstream neighbor is guanine are subject to methylation
> those sites are called CpG sequences
> the enzyme is called DNA methyltransferase (DNMT)
how much of the cytosine bases are methylated?
about 10% in vertebrates
one nucleosome
> how many bp of DNA?
how many histone molecules? which?
>> what happens between nucleosomes?
one nucleosome
> 147 bp of DNA
> wrapped around 8 histone molecules, typicall two of each: H2A,H2B,H3,H4
>> between nucleosomes: variable length stretch of free DNA, stabilized by one molecule of linker histone H1
what changes at histone
> H2B
> H3
> H4
?
H2B: phosphorylation
H3: methylation
H4: acetylation
> acetylation stimulates gene expression
what is the difference between
maintenance methylation
and
de novo methylation
maintenance methylation:
> when DNA is replicated, the newly synthesized strands are methylated based on the methylation of the original strand
de novo methylation:
> newly occuring methylation
is there a relationship between DNA methylation and histone modification?
yes, DNA methylation and histone modification interact
> they may reinforce themselves
what are the 2 best known heritable epigenetic changes?
heritable epigenetic changes?
- x- inactivation
- imprinting
what is genomic imprinting?
genomic imprinting:
only one of a pair of genes, present on homologous chromosomes is expressed, the second being silenced by methylation
>>> always the same member of pair of genes that is imprinted, some genes maternal, some genes paternal gene
> 20-30 human genes known
when does genomic imprinting happen?
how?
silencing usually happens through addition of methyl groups during egg of sperm formation
what are consequences of failed genomic imprinting?
> which known disease?
genomic imprinting is required for normal development
> improper imprinting can result in an individual having two active copies or two inactive copies of a gene
> prader-willi /angelman syndrome both linked to the same imprinted region on chr. 15
> paternal chr silenced: prader-willi syndrome
> maternal chr silenced: angelman syndrome
what are characteristics of prader-willi syndrome?
prader willi syndrome
> facial characteristics
> obesity (relentless appetite)
> hypogonadism (delayed puberty, infertility)
what are characteristics of angelman syndrome?
angelman syndrome
> severe cognitive impairment
> epilepsy
> tremors
> perpetually smiling facial expression, not able to speak
20.000 protein coding genes >>> 150.000 proteins
what 3 mechanisms are responsible for creating ultiple transcripts per locus?
- multiple promoters
- alternative splicing
- RNA editing
how can an additional promotor change the protein a gene is coding for?
> does this change the primary transcript?
the promotor will drive transcription of the gene from an alternative first exon
> yes, the primary transcript is changed
how can alternative splicing change the protein a gene codes for?
alternative splicing can skip one or more exons, include additional internal exons or vary the length of an exon
how does RNA editing change the protein outcome a gene codes for?
RNA editing:
> involves insertion, deletion or modification of specific nucleotides in the primary transcript
what is the relationship between miRNA and cancer?
cancer cells show changes expression of many miRNA’s
> general depression of miRNA levels
the major changes in gene expression are more often due to … than to …?
the major changes in gene expression are more often due to transcription than to translation
how can gene expression be altered at the level of translation?
protein and miRNA complexes can bind to the 3’ UTR region of the mRNA to influence translation
when x-inactivation and imprinting heritable?
when not?
x-inactivation/imprinting
> heritable from cell to cell
> not heritable from parent to offspring
>>> mutations that are heritable from parent to offspring are called “paramutations”
what is the difference between
DNMT1
and
DNMT3A/DNMT3B
?
DNMT1: specifically targets hemimethylated DNA strings
> responsible for maintenance methylation
DNMT3A/DNMT3B: responsible for de novo methylation
what happens with x chrom. when inactivated?
inactivated x chrom remain condensed during the cell cycle
