Ch. 1 - The Cell as a Unit of Health and Disease Flashcards
What are the Classes of Non-Protein Coding sequences ?
- Promoter and Enhancer regions
- Non-coding regulatory RNAs
- Mobile Genetic Elements (transposons, aka Jumping genes)
- Special Structural Regions
What are Promoter and Enhancer regions of DNA?
Regions of DNA that provide binding sites for transcription factors.
What are Noncoding Regulatory RNAs?
Segments of DNA are transcribed into RNAs that are never Translated into proteins
These RNA help regulate gene expression trhough various mechanisms
Examples:
- Micro RNAs
- Long Noncoding RNAs WHICH ARE USED FOR X INACTIVATION
Aside from promoters and enhancers, what else are DNA binding site sequences used for?
There are DNA binding sites for factors that organize and maintain higher order chromatin structures
What are mobile genetic elements?
AKA Jumping Genes
These segments can move around the genome
They are implicated in gene regulation and chromatin organization
Function not well established
EXAMPLE: Transposons
What are special structural regions of DNA?
Telomeres (tips of chromosomes)
Centromeres (chromosome tethers)
What segments of DNA are most involved with polymorphisms/gene variations associated with disease?
Non-Protein coding regions
This indicates that gene regulation may be more important in disease causation than structural changes in specific proteins
What are the two most common forms of DNA variation in the human genome?
Single-Nucleotide Polymorphisms (SNPs)
Copy Number Variations (CNVs)
What are SNPs?
Single Nucleotide Polymorphisms
Variations at SINGLE nucleotide positions
- Almost always Biallelic (only two options exist: A or T)
- Only 1% of SNPs occur in coding regions (as expected by statistics; coding regions make up 1.5% of genome)
What are CNVs?
Copy Number Variants
Consist of 1000 to Millions of base pairs
Can be biallelic (only two options exist, A or T) or very complex rearrangements of genomic material
What is epigenetics?
Heritable changes in gene expression that are not caused by alterations in DNA sequence
Epigenetic alterations are reversible and are amenable to therapeutic intervention
What is a nucleosome?
DNA segments (147 base pairs) long that are wrapped around a histone protein
What is histone?
Protein octamer composed of 4 pair of subunits - H2A, H2B, H3, and H4
Histone molecules are positively charged
Negatively charged DNA strands wrap 1.8 times around each histone molecule forming a beads-n-a-string structure called “Chromatin”
What is Euchromatin and Heterochromatin?
Euchromatin - tightly condensed chromatin DNA that is not being actively transcribed
- Inactive DNA
Heterochromatin - loosely packed chromatin DNA that is being actively transcribed
- Active DNA
What are chromatin remodeling complexes?
Reposition nucleosomes on DNA, exposing or obscuring gene regulatory elements such as promoters
What are Chromatin Writer Complexes?
Carry out histone modifications called “Marks”
Some examples of these modifications include methylation, acetylation, and phosphorylation of specific amino acid residues on the histones
Euchromatin (actively transcribed DNA) are associated with Histone Marks that make DNA accessible to RNA Polymerases
Heterochromatin (inactivated DNA) are associated with Histone Marks that enable compaction of DNA, making it inaccessible to RNA Polymerases
What are Chromatin Erasers?
Histone Marks are reversible due to the actions of Chromatin Erasers (remove the Marks from the Histone molecules)
What are Chromatin Readers?
Proteins that “Read” marks by binding to patterns of Marks and regulate gene expression
What is Histone Methylation?
Specific Chromatin Writers methylate (add methyl group) to Lysine and Arginine residues on Histone molecules
Methylation of Lysine residues can either promote transcriptional activity or repress it depending on the residue that gets methylated
What is Histone Acetylation?
Histone Acetyl Trasnferases (HAT) molecules acetylate (add acetyl groups) to Lysine residues.
Acetylation of Lysine generally causes chromatin to open up and increase transcription activity
This process is reversed by Histone Deacetylases (HDAC), causing chromatin condensation and decrease in transcription activity
What is Histone Phosphorylation?
Serine residues on Histone molecules are phosphorylated (phosphoryl group is added)
Depending on the residue the phosphoryl group is added to, it can either open up the DNA and increase transcription activity, or it can condense the DNA and decrease transcription activity
What is DNA Methylation?
Methyl groups are added to DNA gene regulatory elements
Methylation of DNA typically results in transcriptional silencing
DNA Methylation is tightly regulated by methyltransferases, demethylating enxymes, and methylated-DNA-binding proteins
What are Chromatin Organizing Factors?
Believed to bind to noncoding regions and control long-range looping of DNA
Important in regulating spatial relationships between gene enhancers and promoters that control gene expression
What are miRNAs?
Micro RNA
Do no encode protein, they function primarily to modulate the translation of target mRNAs into their corresponding proteins
Post-translational silencing of gene expression by miRNA is a fundamental and well-conserved mechanism of gene regulation present in all eukaryotes (plants and animals)
22 nucleotides on average in length