Histone and DNA Modifications and Chromatin Remodeling Lecture 3

These flashcards cover the key terms and concepts related to histone modifications, chromatin structure, and gene regulation based on the provided lecture notes.

Chromatin Remodeling

Epigenetic mechanisms that cause alterations of chromatin structure to regulate access to DNA and facilitate transcription.

For nuclear processes to occur, eukaryotic cells must rapidly restructure their chromatin.

1. ATP-Dependent Chromatin remodeling using remodeling protein complexes

   1. SWI/SNF protein complexes

   2. Polycomb Group protein complexes

2. Chemical Modificaitons of histones & DNA

   1. Acetylation

   2. Methylation

3. DNA Methylation

Histone Acetylation

A chemical modification that adds an acetyl group to lysine residues on histone tails, reducing their affinity for DNA and promoting gene expression.

Histone Methylation

The addition of methyl groups to lysine or arginine residues on histones, which can either activate or repress transcription depending on the specific context.

Histone methylation is a dynamic process

• Writers: the methyl groups can be added by methyltransferase

• Erasers: the methyl group can be removed by demethylase enzymes

SWI/SNF Complex

A protein complex that uses ATP to remodel chromatin, facilitating access to DNA for transcription and other nuclear processes.

DNA Methylation

One of the most studied epigenetic mechanisms.

The addition of a methyl group to DNA, primarily occurring on cytosine bases, which is typically associated with gene repression.

In mammalian cells, DNA methylation predominantly occurs on the 5th carbon of cytosine, forming 5-methylcotosine (5-meC)

DNA methylation is catalyzed by de novo methyltransferase (DNMT) enzyme

Epigenetics

The study of heritable changes in gene expression that do not involve changes to the underlying DNA sequence.

Post-Translational Modifications (PTMs)

Chemical modifications occurring after protein translation that can regulate protein functions, such as phosphorylation, acetylation, and methylation.

Readers, Writers, and Erasers

Proteins that add (writers), remove (erasers), or recognize (readers) post-translational modifications on histones.

Writers

• enzymes that add PTMs to histones

Erasers

• enzymes that remove specific PTMs from histone substrates

Readers

• dedicated protein factors that recognize either specific post-translational marks on histones or a combination of marks, and histone variates to direct a particular transcriptional outcome

Acetyltransferases (HATs)

The Writers: Enzymes that add acetyl groups to lysine residues on histone tails, promoting an open chromatin structure and active transcription.

• approx. 30 HATS have been identified in humans

• Grouped into 5 families based on catalytic domain, they interact with different activator and protein complexes

Deacetylases (HDACs)

The Erasers: Enzymes that remove acetyl groups from lysine residues of both histones and non-histone proteins, leading to chromatin condensation and repression of transcription.

• 18 HDACs have been identified in humans

• Grouped into 4 classes based on their sequence homology

• HDACs have relatively low substrate specificity; a single HDAC can act on multiple substrates & multiple HDACs can act on the same substrate

Transcription Activation

The process of initiating gene expression, often facilitated by the loosening of chromatin structure.

Repressive Marks

Histone modifications associated with gene repression, such as H3K27me3 and H3K9me3.

Active Marks

Histone modifications associated with active transcription, such as H3K4me3 and H3 acetylation.

Chromatin Structure

The organization of DNA and histones into a compact, regulated form, critical for DNA accessibility and function.

DNA Methyltransferases (DNMTs)

Enzymes responsible for adding methyl groups to DNA, playing a key role in the establishment and maintenance of DNA methylation.

CpG Islands

Regions of DNA with a high frequency of cytosine and guanine dinucleotides, often associated with gene promoter regions and regulatory regions.

Different types of Histone Chemical Modifications

• Acetylation

• Methylation

• Phosphorylation

• Ubiquitination

These different modifications impact chromatin structure differently

Histone proteins are highly _________ among all eukaryotes and have what two important functions in the cell?

conserved structures

1. Packaging genomic DNA

2. Regulating gene accessibility

DNMT3a & Dnmt3b vs. Dnmt1 functions

• DNMT3a and DNMT3b are de novo methyltransferases that establish new methylation patterns on DNA

• DNMT1 is responsible for maintaining methylation patterns during DNA replication, from parental DNA strand onto the newly synthesized daughter strand

DNA methylation patters are _________ inherited

mitotically inherited and can affect gene expression across generations.

DNA Methylation, Hyper vs. Hypo

are modifications that involve the addition or removal of methyl groups to the DNA molecule, influencing gene expression.

• Hyper-methylation typically silences gene expression

• Hypo-methylation can activate genes

by adding or removing methyl groups

What are some physiological functions of DNA methylations?

DNA methylation plays crucial roles in regulating transcription, gene expression, maintaining genomic stability, and facilitating cellular differentiation. It also contributes to X-chromosome inactivation, aging-related processes, embryonic development & a role in learning and memory.