1.
How ubiquitin and SUMOs
control trx

2.
Why this?
• Ubiquitylation of proteins not only targets
them for destruction, but is also a
regulatory event in the nucleus
• In recent years, important connections
between ubiquitylation, chromatin
structure, signaling pathways and
transcriptional control have emerged.
• The Ub-proteasome system is ideally
suited to controlling the distribution,
abundance and activity of components of
the transcriptional machinery.

3.
Ubiquitylation of histones
• Histone H2A and H2B Ubiquitylation - one of the first recognized
markers of trx active chromatin
• The first ubiquitylated protein to be described was histone H2A
• ubiquitylated forms of histones H2A and H2B were associated specifically with
actively transcribed genes
• Later also H1 and H3 reported to be ubiquitylated

4.
Ubiquitylation and the histone code
• Ubiquitylation of chromatin
• The ubiquitin (Ub)-conjugating
enzyme Rad6 ubiquitylates K123
in the core of histone H2B. This
modification promotes the
methylation of another histone,
H3, at two positions, K4 and K79.
These modifications, in turn, are
required for telomeric-gene
silencing.
• TAFII250 (TFIID component) can
ubiquitylate the linker histone H1;
might relate to the role of this
TAF in transcriptional activation.
• Ubiquitylation = an integral part of
the histone code
 Mechanism?
 Direct structural role by
loosening chromatin structure
 Or as ”tag” recognized by
proteins such as the proteasome
or HDAC6
SEMINAR Inger Louise Bones: Wang et al. (2004) Role of histone
H2A ubiquitination in Polycomb silencing. Nature, 431, 873-878.

5.
Regulating RNAPII by
ubiquitylation

6.
What is SUMO-1 ?
• SUMO-1 (small ubiquitin-related modifier)
• peptide of 101 residues
• function ≠ ubiquitin.
• NOT tagged for degradation
• Rather stabilized or ”targeted” to sub-nuclear
structures

7.
The SUMO-1 protein
• Small Ubiquitin MOdifier
• Link: isopeptide bond
• between the C-terminal glycine
of SUMO and the e-amino group
of a lysine residue in the target
protein.
• Structure
• characteristic ubiquitin-fold +
unique unstructured N-terminal
extension of up to 22 residues -
possible protein interaction
site?
GG
XKE