Question

RECALL What are the major types of covalent modification of histones?

Short answer

The major types of covalent modifications of histones are acetylation, methylation, phosphorylation, ubiquitination, and sumoylation.

Step-by-step solution

- Understand What Histones Are

Histones are proteins that help package DNA into a compact, structured form, which allows it to fit inside the nucleus of a cell. They play a crucial role in gene regulation.

- Identify Covalent Modifications

Covalent modifications are chemical changes to histones that can affect their function. These modifications typically occur on the amino acid residues of histone proteins, often on their N-terminal tails.

- List Major Types of Covalent Modifications

The major types of covalent modifications of histones include: 1. Acetylation: Addition of an acetyl group, usually to lysine residues.2. Methylation: Addition of methyl groups, typically to lysine or arginine residues.3. Phosphorylation: Addition of phosphate groups, generally to serine, threonine, or tyrosine residues.4. Ubiquitination: Addition of ubiquitin, a small protein, usually to lysine residues.5. Sumoylation: Addition of SUMO (Small Ubiquitin-like Modifier) proteins, often to lysine residues.

- Understand Functions of These Modifications

These covalent modifications can modulate interactions between histones and DNA or between histones and other proteins, thereby influencing processes such as gene expression, DNA repair, and chromosome condensation.

Key concepts

Histone Acetylation

Histone acetylation is one of the most vital modifications of histones. It involves the addition of an acetyl group to the lysine residues of histone proteins. This process is generally catalyzed by enzymes known as histone acetyltransferases (HATs). Acetylation neutralizes the positive charge on lysine, which decreases the affinity between the histones and DNA.
This relaxation of the chromatin structure makes DNA more accessible to transcription machinery, thereby promoting gene expression. Conversely, histone deacetylases (HDACs) remove these acetyl groups, leading to chromatin condensation and reduced gene expression.

Histone Methylation

Histone methylation is the addition of one, two, or three methyl groups to lysine or arginine residues on histone proteins. Unlike acetylation, methylation does not change the charge of histones but can either promote or repress gene expression depending on which residue is methylated and the number of methyl groups added.
Enzymes called histone methyltransferases (HMTs) add methyl groups, while demethylases remove them. For example, methylation of histone H3 on lysine 4 (H3K4me) is often associated with active transcription, whereas methylation of histone H3 on lysine 27 (H3K27me) is linked to gene repression.

Histone Phosphorylation

Histone phosphorylation involves the addition of phosphate groups to serine, threonine, or tyrosine residues. This modification is often related to cellular processes such as DNA damage repair and cell division. Enzymes known as kinases add phosphate groups, while phosphatases remove them.
Phosphorylation introduces a negative charge on histones, leading to changes in chromatin structure. For instance, phosphorylation of histone H2A at serine 139, known as H2AX, plays a crucial role in recruiting DNA repair machinery to sites of DNA damage.

Histone Ubiquitination

Histone ubiquitination involves the attachment of a small protein called ubiquitin to lysine residues on histone proteins. This process is facilitated by a series of enzymes: E1 (activating enzyme), E2 (conjugating enzyme), and E3 (ligase).
Ubiquitination can serve various functions, such as signaling for protein degradation, altering protein activity, or changing chromatin structure. For instance, ubiquitination of histone H2B at lysine 120 (H2BK120ub) is an essential step for the subsequent methylation of histone H3 on lysine 4, thus influencing transcription.

Histone Sumoylation

Histone sumoylation involves the attachment of SUMO (Small Ubiquitin-like Modifier) proteins to lysine residues. This modification is catalyzed by SUMO-specific enzymes and is typically linked to gene repression.
Unlike ubiquitination, sumoylation rarely marks proteins for degradation. Instead, it can influence chromatin organization, transcriptional repression, and DNA repair. For example, sumoylation of histone H4 is crucial for maintaining genomic stability and preventing unscheduled recombination events.