Summary Study Notes Fundamentals of Genetics | Week 2 | Wageningen University

Fundamentals of genetics week 2
Ch 12 regulation of transcription in eukaryotes
12.1 Transcription factors regulate transcription
 Trans-acting regulatory proteins and cis-acting regulatory DNA sequences
 The regulatory proteins can be divided into two sets, those that directly bind DNA and
those that do not
o Transcription factors that directly bind regulatory DNA sequences called
enhancers (proximal (of promoter) or distal)
o Coregulators, which do not directly bind DNA  through biding or enzymatically
modifying other transcription regulatory factors
 Coactivators increase the amount of transcription
 Corepressors decrease the amount of transcription
 Transcription factors bind distal and proximal enhancers
 Hundreds to thousands of base pairs upstream or downstream of the transcription
start site
 Transcription factors used their DNA binding activation/repression, dimerization, and
ligan-binding domains to activate or repress gene transcription
 Some GTFs directly bind DNA regulatory sequences within core promoters that
surround transcription start sites
Transcription factors bind distal and proximal enhancers
 General features of enhancers:
o Short sequence elements (6-10 base pairs)
o Multiple elements are often clustered together
 Enhancer elements frequently occur as inverted repeats of the same DNA sequence
for binding of two similar or identical transcription factors
 Transcription factors also bind to other proteins
 Dimerization domain: facilitates the formation of homodimers (binding between two
C/EBP proteins) and hetetrodimers (binding between different C/EBP family
members)
 DNA-biding domain: the site on a DNA-binding protein that directly interacts with
specific DNA sequences
 Activation domain: interacts with other components of the transcription machinery to
turn on transcription
 Repression domains: use similar mechanisms to turn off transcription
 Ligand-binding domain: that binds a ligand such as a hormone or a vitamin, changing
the structure of the transcription factor and activating it
 Transcription factors coordinately regulate the transcription of multiple
genes involved in the same biological process by binding enhancers
that are common to the genes
 The ability of Gal4 to function in a variety of eukaryotes indicates that
eukaryotes generally have common transcription regulatory
machineries and mechanisms
 Gal4 (transcription factor) coordinately regulates the transcription of
multiple genes by binding enhancers that are common to the genes
 Eukaryotic transcription factors are modular, having separable
domains for DNA binding, activation/repression, dimerization, and
ligand-binding

,  Environmental signals such as galactose alter the activity of eukaryotic transcription
factors by controlling their interactions with
other proteins
 The control of yeast mating type is an
example of how cell type-specific patterns
of transcription in eukaryotes can be
governed by different combinations of
interacting transcription factors
12.2 Chromatin structure
 In eukaryotes, DNA is packaged with
histones in chromatin, nucleosomes, the
units of chromatinm contain two copies of each of the core histones (H2A, H2B, H3
and H4) around which is wrapped 146 base pairs of DNA. Complete nucleosome also
contain histone H1 and linker DNA of variable length
 Regions of the genome with few genes, such as centromeres and telomeres, are
compacted into heterochromatin throughout the cell cycle, whereas regions that are
generich vary in their level of chromatin compaction. Typically genes are
transcriptionally silent when compacted into heterochromatin, and they can be
transcriptionally active when less compacted into euchromatin
 The wrapping of DNA enhancer elements into nucleosomes can prevent binding by
transcription factors. Insulators prevent enhancers and their associated transcription
factors from activating the transcription of genes outside a TAD (topological
associated domains)
12.3 Chromatin regulates transcription
 Chromatin is made up of nucleosomes that fold upon one another into a compact
filament
 Chromatin modification: altering the chemical structure of amino acids in histones or
nucleotides in DNA to affect recruitment of transcription factors, coregulators and
general transcription factors to chromatin
 Chromatin remodeling: changes accessibility of DNA to transcription factors co-
regulators and general GTFs
 Acetylation of lysines in histones by HATs (1) loosens interactions within and between
nucleosomes and (2) creates a binding site for bromodomain, found in some
transcription coregulators
 Transcription is regulated by chemical modifications of amino acids in histones and
nucleotides in DNA. Modifications are added by writer enzymes, removed by eraser
enzymes, and bound by reader proteins
 The histone code hypothesis posits that different combinations of histone
modifications create unique binding sites that can be read by transcription
coregulators, thereby conferring a variety of transcriptional outcomes
 Methylation of cytosine in CpG islands at gene promoters is correlated with the
repression of transcription. Like modifications of histone proteins, CpG methylation of
DNA represses transcription by altering the affinity of transcription factors,
coregulators, and general transcription factors for chromatin
 Unmethyladed CpG islands at promoters are generally correlated with open
chromatin and active transcription
 Changing histone0DNA interactions in nucleosomes to render DNA either more or
less accessible to transcription regulators