lo 2 The histone code hypothesis

Who proposed the histone code hypothesis?

Brian D. Strahl and C. David Allis

What is the histone code hypothesis?

Post-translational modifications of histone proteins act sequentially or in combination

to form a 'histone code'

that is read by other proteins

to bring about distinct downstream events

What are the three categories of key regulators of histone modifications?

Writers, readers, and erasers

Give examples of histone modification "writers"

Lysine acetyltransferases (KAT) - P300 and CBP;

Lysine methyltransferases (KMT) - KMT2D and EZH2

Give examples of histone modification "erasers"

Histone deacetylases (HDAC) - HDAC1

Lysine demethylases (KDM) - KDM6A

Give examples of histone modification "readers"

Bromodomain (BRD) proteins - BRD4 and BRD9;

Plant homeodomain (PHD) proteins - PHF19

What type of proteins are p300 and CBP?

Histone acetyltransferases (HATs) / Lysine acetyltransferases (KATs)

What does acetylation of histone tails do to the charge of histones?

It neutralizes the positive charge

How does acetylation of histone tails affect chromatin state?

It weakens the interaction between histones and negatively charged DNA, making access to enzymes and other effectors possible

What does increased acetylation correlate with?

Transcriptional activity

What do bromodomain proteins bind to?

Acetylated histones

What is the role of bromodomain proteins when they bind to acetylated histones?

They promote transcription and recruit RNA Pol II machinery

What was discovered in the late 1990s and early 2000s regarding histones?

Many histone modifying activities were discovered

Which histone acetyltransferases were identified as transcriptional coactivators in 1996?

p300 and CBP

How does histone acetylation neutralize the negative charge of DNA?

Acetylation neutralizes the positive charge of histone tails, weakening their interaction with negatively charged