Dunn M&C - Eukaryotic Transcriptional Regulation

interphase (euk.)

chromatin can be packaged/condensed differentially — this impacts transcription

chromatin

• 50% wt DNA and 50% wt protein (histones)

• condenses 2m of linear DNA into a ~1μm nucleus

• impedes transcription

• looped domains is stablized by a protein scaffold

more nuclease sensitive

more transcribable

less nuclease sensitive

less transcribable; more nuclease resistant

histones

proteins that package and compact DNA within the cell nucleus, forming the basic structural units of chromatin

• eight of these in a nucleosome

heterochromatin

interphase: type of chromatin; tightly packed and transcriptionally inactive/silent.

• e.g, centromeres and telomeres (both don’t contain genes)

• associated with deacetylated histones

• can be interconverted by enzymes, and nucleosomes can be pushed around relative to the DNA

euchromatin

interphase: type of chromatin; loosely packed and transcriptionally active/competent

• associated with acetylated histones

• can be interconverted by enzymes, and nucleosomes can be pushed around relative to the DNA

centromeres

used to divide duplicate chromosomes between cells during division

heterochromatin and euchromatin interconverted

chromatin remodeling

eukaryotic chemical mod.

DNA undergoes methylation on cytosine residues within CpG (CG) sequences, the most common chemical modification to DNA in the euk.

CpG methylation

gene promoter region usually brings about heterochromatinization and transcriptional silencing of the gene

CpG island

a region of concentrated CGs that often occurs near or within a promoter

methylation of a CpG island

Can change over time or in response to environmental cues, providing a way to turn genes on or off.

• repression of a gene is often accompanied by heavy methylation of a nearby island

histone tails

protrudes from the nucleosome and undergo post-translational modification, which controls what happens to that DNA

• poorly structured “floppy” N-terminal portions of histone proteins

• DNA near them is regulated by them

histone modification

can regulate transcription (and any DNA-dependent process) in different ways — sometimes, they influence the way chromatin folds

• sometimes recruit a protein that brings about a change, like increasing transcription rate

• DNA near the tails is regulated by them

combinatorial control

a transcription factor has its effect based on its combination w/ others

• much more extensive in multicellular organisms

• e.g, E.coli — regulation of the lac operon by two transcription factors based on two factors— glucose levels and lactose levels

X inactivation

the heterochromatinzation of one X chromosome occurs in XX female mammals as a gene dosage compensation mechanism

• dosage of x-linked genes would be 2x as great in females as in males were it not for this dosage compensation mechanism.

• x chromosome selected at random

dosage compensation mechanism

the process by which organisms equalize the expression of genes between members of different biological sexes.

• Across species, different sexes are often characterized by different types and numbers of sex chromosomes

epigenetic inheritance

cell division continues, the inactive X stays inactive

• in each cell lineage, the same X chromosome that was originally inactivated remains inactive

• what is being inherited is the silent chromatin state rather than DNA sequence

XX females

mosaics for their X chromosome alleles

biological mosaic

an organism, like a human, that has two or more genetically distinct cell populations, meaning they have different combinations of chromosomes

non-coding RNA Xist gene

plays a crucial role in X-chromosome inactivation (XCI) in mammals. It's transcribed from the inactive X chromosome.

• brings about heterochromatinization

• heterochromatinizing enzymes are trans factors

• Xist is a cis factor

histone acetylation

associated with transcriptionally active/competent chromatin