Hierarchies in eukaryotic

genome organization

Dr. Sandeep Kumar

Assistant Professor,
Dept. of Life Sciences
Jain (Deemed-to-be) University
Organization of Eukaryotic Chromosome
Eukaryotic chromosomes
• Individual eukaryotic chromosomes contain
enormous amounts of DNA.
• Like the bacterial chromosome, each
eukaryotic chromosome consists of a
single, extremely long molecule of DNA.
• For all of this DNA to fit into the nucleus,
tremendous packing and folding are
required, the extent of which must change
in the course of the cell cycle
Chromatin

• Eukaryotic DNA in the cell is closely

associated with proteins.
• This combination of DNA and protein is called
chromatin.
• The two basic types of chromatin are
euchromatin, which undergoes the normal
process of condensation and decondensation
in the cell cycle,
• Heterochromatin, which remains in a highly
condensed state throughout the cell cycle,
even during interphase
Heterochromatin
• All chromosomes have
heterochromatin at the
centromeres and telomeres.
• Heterochromatin is also
present at other specific places
on some chromosomes, along
the entire inactive X
chromosome in female
mammals and throughout most
of the Y chromosome in males.
Histone proteins
• Most abundant proteins in chromatin
• Family of highly basic proteins whose primary
job is to associate with DNA and condense the
chromatin
• Rich in positively charged amino acids such as
lysine and arginine
• Their positive charges allow them to associate
with the negatively charged DNA with greater
affinity
• Histone proteins fall into two major
categories: core histones and linker histones
Histone proteins
Nonhistone chromosomal proteins

• May regulate gene expression in eukaryotic cells

• New species of nonhistone chromosomal proteins as well as
modifications of preexisting nonhistone chromosomal proteins
are involved in the control of transcription.
• The nonhistone chromosomal proteins include
1. enzymes that have a general function - HDAC
2. proteins that are involved in determining the structure of
chromatin - structural maintenance of chromosomes
3. proteins that serve as recognition sites for binding of
regulatory macromolecules – activator and repressor proteins
Nucleosome

• The simplest level is the

double-helical structure of DNA and
chromosome – advanced
• Such experiments demonstrated
that chromatin is not a random
association of proteins and DNA but
has a fundamental repeating
structure.
• The repeating core of protein and
DNA produced by digestion with
nuclease enzymes is the simplest
level of chromatin structure, the
nucleosome
Structure of Histones

• All core histones share two

common structural domains:
• The histone fold domain
• about 70 amino acids
• Structurally conserved motif
found near the C-terminus
• The histone tail, rich in lysine
residues – post translation
modifications
Histone H1
• The fifth type of histone, H1, is
not a part of the core particle but
plays an important role in
nucleosome structure.
• H1 binds to 20 to 22 bp of DNA
where the DNA joins and leaves
the octamer and helps to lock the
DNA into place, acting as a
clamp around the nucleosome
octamer
Higher-order chromatin structure

• Adjacent nucleosomes pack

together to form a 30-nm
• nucleosomes fold on themselves to
form a dense, tightly packed structure
that makes up a fiber with
a diameter of about 30 nm
• Two different models have been
proposed for the 30-nm fiber: a
solenoid model, in which a linear array
of nucleosomes are coiled, and a helix
model, in which nucleosomes are
arranged in a zigzag ribbon that twists
or supercoils.
Nuclear scaffold

• The next-higher level of chromatin structure

is a series of loops of 30-nm fibers, each
anchored at its base by proteins in the
nuclear scaffold
• On average, each loop encompasses some
20,000 to 100,000 bp of DNA and is about
300 nm in length, but the individual loops
vary considerably.
• The 300-nm loops are packed and folded to
produce a 250-nm-wide fiber. Tight helical
coiling of the 250-nm fiber, in turn, produces
the structure that appears in metaphase—
individual chromatids approximately 700 nm
in width