Chromatin and Epigenetics

What is chromatin?

Chromatin is a complex of DNA and proteins (histones and non-histones) found in eukaryotic cells.

What are the two types of proteins in chromatin?

Histones and non-histones.

Name the four core histones

H2A, H2B, H3, and H4.

What is the function of histone H1?

Histone H1 binds to linker DNA to help condense chromatin into the 30nm fiber.

What is a nucleosome

A nucleosome is the basic unit of chromatin, consisting of DNA wrapped around a histone octamer (two each of H2A, H2B, H3, and H4).

How much DNA is wrapped around a nucleosome core

Approximately 146 base pairs

What is the "beads on a string" structure?

It refers to the nucleosomes (beads) connected by linker DNA (string).

What is the role of MARs (Matrix Attachment Regions)?

MARs flank transcriptionally active genes and help regulate gene expression by anchoring DNA loops to the nuclear matrix.

What is the difference between euchromatin and heterochromatin

Euchromatin is less condensed and transcriptionally active, while heterochromatin is highly condensed and transcriptionally inactive.

What is chromatin remodeling

Chromatin remodeling is the process of altering chromatin structure to make DNA more or less accessible for transcription.

Name two mechanisms of chromatin remodeling.

Sliding and transfer of nucleosomes.

What is the role of SWI/SNF complexes

SWI/SNF complexes are chromatin remodeling complexes that use ATP to reposition nucleosomes.

What is histone acetylation

Histone acetylation is the addition of acetyl groups to lysine residues on histone tails, which reduces their positive charge and loosens chromatin structure.

What is the effect of histone acetylation on chromatin

It is associated with euchromatin and increased gene expression.

What is histone methylation?

Histone methylation is the addition of methyl groups to lysine or arginine residues on histone tails.

What is the effect of histone methylation on chromatin

It can either activate or repress gene expression, depending on the specific residue methylated.

What is histone phosphorylation

Histone phosphorylation is the addition of phosphate groups to serine or threonine residues on histone tails.

What is the role of histone deacetylases (HDACs)?

HDACs remove acetyl groups from histones, leading to chromatin condensation and gene repression.

What is the role of histone acetyltransferases (HATs)?

HATs add acetyl groups to histones, leading to chromatin relaxation and gene activation.

What is the significance of histone tail modifications?

Histone tail modifications regulate chromatin structure and gene expression.

What is the role of chromatin structure in gene regulation?

Chromatin structure determines the accessibility of DNA to transcription factors and other regulatory proteins.

What happens to chromatin during mitosis?

Chromatin becomes highly condensed to form visible chromosomes.

What is the role of chromatin in cell differentiation?

Chromatin remodeling and histone modifications play a key role in turning genes on or off during differentiation.

What is the relationship between chromatin structure and aging?

Aging leads to a loss of chromatin regulation, resulting in increased mutations and disease risk.

What diseases are associated with chromatin remodeling defects?

Cancer, among others, is associated with defects in chromatin remodeling complexes like SWI/SNF.

What is DNA methylation

DNA methylation is the addition of a methyl group to the 5th carbon of cytosine, typically in CpG dinucleotides.

Where does DNA methylation commonly occur in the genome

DNA methylation commonly occurs at CpG islands, particularly in promoter regions.

What is the effect of DNA methylation on gene expression

DNA methylation typically represses gene expression by preventing transcription factor binding

What enzyme catalyzes DNA methylation

DNA methyltransferases (DNMTs) catalyze DNA methylation.

Name three DNA methyltransferases

Answer: DNMT1, DNMT3A, and DNMT3B.

What is the role of MeCP2

MeCP2 recognizes methylated DNA and recruits histone modifiers and chromatin remodeling proteins to repress gene expression.

What happens when DNA methylation is lost globally?

Global loss of DNA methylation can lead to unwanted gene expression and chromosomal instability.

What is the relationship between DNA methylation and cancer

Hypermethylation of tumor suppressor genes or hypomethylation of oncogenes can lead to cancer.

What is Rett syndrome?

Rett syndrome is a rare genetic disorder caused by mutations in the MeCP2 gene, leading to severe autism and developmental issues.

What is X-inactivation?

X-inactivation is the process by which one of the two X chromosomes in females is randomly inactivated to achieve dosage compensation.

What is the role of Xist in X-inactivation?

Answer: Xist is a non-coding RNA that initiates X-inactivation by coating the X chromosome and recruiting silencing factors.

What is genomic imprinting?

Genomic imprinting is the phenomenon where certain genes are expressed in a parent-of-origin-specific manner.

What is an example of a disorder caused by imprinting defects?

Prader-Willi syndrome and Angelman syndrome are caused by imprinting defects on chromosome 15

What is Beckwith-Wiedemann syndrome?

Beckwith-Wiedemann syndrome is a developmental disorder caused by deregulation of imprinted genes on chromosome 11.

What is the role of the ICR (Imprinting Control Region)?

The ICR regulates the expression of imprinted genes by controlling DNA methylation and insulator binding.

What is epigenetics?

Epigenetics refers to heritable changes in gene expression that do not involve changes to the DNA sequence.

What are the main mechanisms of epigenetics?

DNA methylation, histone modification, nucleosome positioning, and non-coding RNA.

How does DNA methylation affect chromatin structure?

DNA methylation recruits proteins like MeCP2, which can modify histones and condense chromatin.

What is the role of epigenetics in development?

Epigenetics regulates gene expression during development, influencing cell differentiation and tissue formation.

What is the Agouti mouse model?

The Agouti mouse model demonstrates how environmental factors (like diet) can influence epigenetic changes and phenotype.

What is the effect of methyl-donating supplements on Agouti mice?

Methyl-donating supplements can silence the Agouti gene, leading to healthier offspring with brown fur.

What is the role of epigenetics in disease?

Epigenetic changes can contribute to diseases like cancer, diabetes, and obesity.

How can environmental factors influence epigenetics?

Environmental factors like diet, stress, and toxins can alter DNA methylation and histone modifications.

What is the role of epigenetics in the fetal environment?

Epigenetic changes during fetal development can influence long-term health and disease risk

What is the relationship between epigenetics and behavior?

Epigenetic changes can influence behavior by altering gene expression in response to environmental stimuli.

What is the central dogma of molecular biology?

The central dogma describes the flow of genetic information: DNA → RNA → Protein.

What is the role of chromatin in DNA replication?

Chromatin structure must be relaxed to allow access to the replication machinery.

What is the role of chromatin in transcription?

Chromatin must be relaxed to allow RNA polymerase and transcription factors to access DNA.

What is the role of non-histone proteins in chromatin

Non-histone proteins help regulate chromatin structure and gene expression.

What is the role of histone variants?

Histone variants can replace core histones to alter chromatin structure and function.

What is the role of chromatin in stem cells?

Stem cells have more relaxed chromatin (euchromatin) to maintain pluripotency.

What is the role of chromatin in differentiated cells?

Answer: Differentiated cells have more condensed chromatin (heterochromatin) to maintain cell identity.

What is the role of chromatin in aging?

Aging leads to a loss of chromatin regulation, resulting in increased mutations and disease risk.

What is the role of chromatin in cancer?

Chromatin remodeling defects can lead to uncontrolled cell growth and cancer.

What is the role of chromatin in response to external stimuli?

Chromatin remodeling allows cells to rapidly change gene expression in response to environmental changes.

What is the role of DNA methylation in gene silencing?

DNA methylation can silence genes by preventing transcription factor binding and recruiting repressive proteins.

What is the role of histone modifications in gene activation?

Histone modifications like acetylation can relax chromatin and promote gene activation.

What is the role of histone modifications in gene repression?

Histone modifications like methylation can condense chromatin and repress gene expression.

What is the role of non-coding RNA in epigenetics?

Non-coding RNAs can regulate gene expression by interacting with chromatin and recruiting modifying enzymes.

What is the role of epigenetics in cellular memory?

Epigenetic marks can maintain gene expression patterns across cell divisions, allowing cells to "remember" their identity.

What is the role of epigenetics in environmental adaptation?

Epigenetic changes allow organisms to adapt to environmental changes by altering gene expression.

What is the role of epigenetics in evolution?

Epigenetic changes can influence phenotypic variation and contribute to evolutionary processes.

What is the role of epigenetics in disease prevention?

Understanding epigenetics can lead to new therapies for diseases like cancer and diabetes.

What is the role of epigenetics in aging?

Epigenetic changes accumulate with age and contribute to age-related diseases.