module 9 Flashcards
Epigenetics
the study of mechanisms that lead to changes in gene expression that can be passed from cell to cell and are reversible, but do not involve a change in the sequence of DNA
genes can be targeted for epigenetic regulation via
transcription factors and noncoding RNA
cis-epigenetic changes
are maintained at a specific site during cell division
trans-epigenetic changes
are maintained by diffusible factors, such as transcription factors
epigenetic gene regulation may occur as/be caused by
programed developmental change (genomic imprinting, x-chromosome inactivation, cell differentiation) or environmental agents (temperature, diet, toxins)
euchromatin
chromosomal regions that are not stained during interphase, loop domains are not tightly packed, transcriptionally active
heterchromatin
chromosomal regions that are stained during interphase, great level of compaction, inhibitory effect on gene expression
constitutive heterochromatin
regions that are heterochromatic at the same location in all cell types
facultative heterochromatin
heterochromatin that varies in its location among different cell types, allows for tissue specific gene regulation
the genes that are contained with facultative heterochromatin are
usually silenced
constitutive heterochromatin characteristics
close to centromere or telomere, generally composed of many short tandemly repeated sequences, highly methylated on cytosines in vertebrates and plants, H3K9me3 common in animals, H3K9me2 in plants
facultative heterochromatin characteristics
formation is reversible, multiple sites between the centromere and the telomere, LINE-type repeats, methylation at CpG islands in gene regulatory regions (silences genes), H3K9me3 common
Post-translational modifications (PTMs)
result in changes in chromatin structure, such as heterochromatin formation
reader domains
bind specific proteins to particular PTMs in nucleosomes
writer domains
addition of PTMs
Eraser domains
remove PTMs
recruitment domains
recruit other proteins, such as chromatin remodelers or chromatin-modifying enzymes
heterochromatin formation involves multiple molecular events:
post-translational modifications of histones, binding of proteins to nucleosomes, chromatin remodeling, DNA methylation, binding of non-coding RNAs
higher-order structural features of heterochromatin
- has closer, more stable contacts of nucleosomes with each other via HP1 2. forms closer loop domains, binds to the nuclear lamina 3. may undergo liquid-liquid phase separation
Nucleation
short chromosomal site bound by chromatin-modifying enzymes and chromatin-remodeling complexes
Spreading
adjacent euchromatin is turned into heterochromatin
Barrier
in interphase chromosomes, spreading stops when it reaches a barrier (common: Nucleosome free region)
heterochromatin structure is maintained by
DNA methylation, histone modifications, DNA polymerase, local chromatin structure
pioneer factors
category of transcription factors, can recognize and bind to DNA sequences exposed on the surface of a nucleosomes
pioneer factors can
- recruit chromatin-remodeling complexes and histone-modifying enzymes that carry out epigenetic changes
- influence the ability of other transcription factors to bind to enhancer sequences
- decrease the level of DNA methylation by binding to CpG islands thereby blocking DNA methyltransferases
- be apart of gene activation/silencing
Trithorax group (TrxG)
involved with gene activation
Polycomb group (PcG)
involved with gene repression, two types: PRC1 and PRC2
chromatin compaction
PRC1 may cause nucleosomes in the target gene to form a knot-like structure
covalent modification of histones
PRC1 may covalently modify histone H2A by attaching ubiquitin molecules
direct interaction with a transcription factor
PRC1 may directly inhibit proteins involved with transcription
noncoding RNA functions
- scaffold, binds to a group of proteins
- guide, binds to a protein and guides it to a specific site in the cell
- alteration of protein function or stability, binds to protein and alters structure
- ribozyme, acts as a catalyst
- blocker, physically prevents a cellular process from happening
- decoy, recognizes another ncRNA and sequesters it
types of ncRNA
long ncRNA (IncRNA), small regulatory RNA (short ncRNA), MicroRNA
double-stranded RNA is ______ potent at silencing mRNA than antisense RNA
more
RNA interference
the phenomenon in which double-stranded RNA causes the silencing of mRNA
iRNA is mediated by
microRNAs and small interfering RNAs
microRNAs
transcribed from endogenous eukaryotic genes (pri-miRNA) regulate gene expression
siRNA
originates from exogenous sources (not made by cells) but can come from viruses
RNA-Induced Silencing Complex (RISC)
- inhibits translation without degrading mRNA
- degradation of the mRNA through cleavage of Argonaute
CRISPR-Cas System
defense against bacteriophages, plasmids, and transposons
CRISPR-Cas System defense phases
- Adaption
- Expression
- Interference
Adaption phase
Cas protein complex cleaves bacteriophage DNA and inserts it into Crispr gene
Expression phase
exposure to bacteriophage results in the expression of crispr, tracr, and Cas9 genes
Interference phase
Cas system is able to recognize and bind to bacteriophages and inhibit proliferation
