Hst 6: gen regulatie en epigenetica Flashcards
CIs-acting regulatorische DNA element
- DNA sequentie
- functie is gen reguatie
- beperkt tot dna molecule waar het op gelegen is
- vb: gen promotor
- heeft effect op één allel (vb enkel vader)
boek p 151
promoters, cis-acting regulatory DNA sequences
that are important in establishing which segments of a DNA strand will
be transcribed. Each promoter is a collection of very short sequence elements
that are usually clustered within a few hundred nucleotides from
the transcription start site. For each DNA strand, transcription begins at
fixed points on the DNA where the chromatin has been induced to adopt
an ‘open’ structure (see below).
Nuclear genes are transcribed by
NCBI
In eukaryotes, we distinguish between two classes of cis-acting elements that can exert their effects at considerable distance from the promoter. Enhancers are cis-acting sequences that can greatly increase transcription rates from promoters on the same DNA molecule; thus, they act to activate, or positively regulate, transcription. Silencers have the opposite effect. Silencers are cis-acting sequences that are bound by repressors, thereby inhibiting activators and reducing transcription. Enhancers and silencers are similar to promoter-proximal regions in that they are organized as a series of cis-acting sequences that are bound by trans-acting regulatory proteins. However, they are distinguished from promoter-proximal elements by being able to act at a distance, sometimes 50 kb or more, and by being able to operate either upstream or downstream from the promoter that they control
CIs-acting regulatorische RNA element
- RNA sequentie
- functie is regulatie van een enkelvoudige RNA transcript waar het op gelegen is
- vaak gelegen in untraslated regio (3’ of 5’ UTR) van mRNA
- miRNA binden op 3’ UTR
intechopen:
Cis-acting regulatory sequence elements are subsequences contained in the 5′ untranslated region (UTR), 3′ UTR, introns, and coding regions of precursor RNA and mature mRNA that are selectively recognized by a complementary set of one or more trans-acting factors to regulate posttranscriptional gene expression.
Trans-acting factors include RNA-binding proteins (RNA-BPs) and microRNAs (miRNAs), which are able to influence the fate of mRNA by controlling processes such as translation and mRNA degradation (reviewed in Refs. [
Trans-acting gen regulator
- regulatorische eiwit OF RNA molecule
- migreert door diffuse , herkent en bindt korte NZ sequenties (op DNA of RNA)
- reguleert de expressie van beide allelen
Cis en trans regulatie
vaak is er een combinatie van cis en trans regulatie : vb: een transcriptie factor (trans regulator) bindt op een enhancer (cis regulator)
vb: miRNA (trans regulator) bint op miRNA bindende sequentie (cis regulator).
RNA polymerase II
* schrijft af > eiwit coderende genen >long ncRNA >miRNA * vormt zich op consensusequenties nabij de promotor
Enhancers
- bindingsite voor transcriptie factoren
- vaak niet nabij transcriptie site-> het dna waar het op effect heeft wordt uit gelooped zodat enhancers kunnen interagegeren met eiwitten (het rna polymerase complex) op de promotor van target gen
- versterken expressie
- kunnen
https: //www.youtube.com/watch?v=k26xwzJpVAc&ab_channel=MoofUniversity
Silencers
*silencers zijn cis-acting DNA elementen die verantwoordelijk zijn voor het onderdrukken van expressie, wanneer ze actief zijn.
Boundaries elements
*barriere elementen tussen euchromatine en heterochromatine
transcriptie factoren
- binden nabij of op cis-regulerende DNA
- meerdere TF kunnen tegelijk binden
- herkennen een korte sequentie dna, en binden met zinkvingers of leucine zippers
- kunnen enkel binden als DNA ontspannen genoeg is en werkt vaak enkel als een combinatie van TF binden
Geef het verschil tussen Insulators en barrier elements
Some boundary elements act as barriers between neighboring
euchromatin and heterochromatin regions. Another type is an insulator
that can block inappropriate interactions between enhancers and promoters
by binding regulatory proteins, notably the CTCF regulator
Barrier elements are DNA sequence elements that prevent inappropriate interactions between adjacent chromatin domains. One type of
A barrier
element protects genes in the euchromatin
region from being silenced by adjacent
heterochromatin (shown here in green). Largescale
rearrangements, such as the inversion
shown here, can relocate the protective barrier
element so that it no longer separates gene A
from a neighboring heterochromatic region. This
allows heterochromatinization of what had been a
euchromatic region, resulting in gene silencing
(a position effect).
TADs
Wiki
A topologically associating domain (TAD)
self-interacting genomic: DNA sequences within a TAD physically interact with each other more frequently than with sequences outside the TAD.
Boundaries at both side of the these domains are conserved between different mammalian cell types and even across species[2] and are highly enriched with CCCTC-binding factor (CTCF) and cohesin binding sites.
Most of the studies indicate TADs regulate gene expression by limiting the enhancer-promoter interaction to each TAD
Disruption of TAD boundaries is found to be associated with a wide range of diseases such as cancer,[7][8][9] variety of limb malformations such as synpolydactyly, Cooks syndrome, and F-syndrome,[10] and number of brain disorders like Hypoplastic corpus callosum and Adult-onset demyelinating leukodystrophy.[10]
DNA bindings motieven
- gebruikt door TF en andere dna-bindende eiwitten
- zinc-vinger motief -> zn2+ opn bindt op 4 geconserveerde AZ. Bevat alfa en beta helix/alfa helix samengehouden door zink ion
*binden op grote groeve
——
leucine zipper
*leucines aan een kant van helix
*vormt samen met een tweede helix een knijper structuur
The leucine zipper is another common motif found in many DNA-binding proteins, including transcription factors.
The leucine zipper is an amphipathic a helix containing heptad repeats of Leu residues on one face of the helix and serves as a dimerization module.
Geef de belangrijkste onderdelen voor RNA splicing
*3 rna sequenties fundamenteel aanwezig > splice donor en acceptor >branche site >domeinen die splicing stimuleren/inhibieren >spliceosoom
Splicosoom
- verantwoordelijk voor het verwijderen van intronen in pre-mRNA.
- bestaat uit small nucleair RNA (snRNA)
- snRNA zullen basenparen met met branch site sequenties, splice donor sequenties en splice acceptor sequenties
Splice donor en Splice acceptor
- Donor bevat invariante GU dinucleotiden aan de 5’ uiteinde van intron op RNA
- Acceptor bevat invariante AG dinucleotide op 3’ uiteinde van intron
