Chromosomal Structure

Question 1

What is the difference between chromosomes and chromatin?

Answer 1

chromosomes: 23 pairs of packages of long double stranded DNA wrapped around histone proteins molecules found in the nucleus

chromatin: complex of DNA, histones, and non-histone chromosomal proteins in chromosomes

Question 2

What are histones?

Answer 2

Abundant, highly conserved proteins which DNA wraps around to form nucleosomes.

Question 3

How do histones wrap around DNA?

Answer 3

Positive charges of N terminus tail of histones associate tightly to negatively charged phosphate backbone of DNA

Question 4

What is a nucleosome’s structure and function?

Answer 4

Structure: DNA wrapped around octameric core of histone

Function: basic structural unit of DNA packaging in eukaryotes that convert interphase DNA to chromatin fibers.

Question 5

What are the 4 levels of DNA organization?

Answer 5

1. “Beads on a string” form of chromatin
2. 30nm chromatin fiber
3. chromatin fiber folded into loops
4. Loops folded into more loops creating chromosome

Question 6

What is the first level of DNA structure?

Answer 6

“Beads-On-A-String” form:

Beads made of H2A, H2B, H3 an H4 histones are wrapped with 147-nucleotide pair DNA double helix and linked together by a linker DNA.

Question 7

What is the second level of DNA structure?

Answer 7

Long strings of Histones and DNA are condensed into 30nm thick chains by linker histone H1.

Question 8

How many histones do eukaryotes have?

Answer 8

A pair of 4 types of histones: HA, H2B, H3 and H4

Question 9

What is Histone H1?

Answer 9

Linker histone that links adjacent nucleosome core particles.

Question 10

What is the third level of DNA organization?

Answer 10

Conversion of linear chromatin fiber to chromatin loops extending from the center of the chromosome via phosphorylation of SMC ring complex.

Question 11

How do chromatin loops form?

Answer 11

1. SMC ring complex (specifically cohesin) encircles and attaches to DNA double helix
2. Two ATP hydrolyze which breaks open the complex, widening grip on DNA.
3. ADP on ring is released and ring closes again, sliding the protein further from where it originally was and sliding more DNA to the loop.
4. Cohesin travels along DNA until they run up against sequence-specific clamp protein which bind together to prevent further looping

Question 12

What is cohesin?

Answer 12

Ring shaped SMC protein complex that organizes interphase chromosomes into a long series of large chromatin loops and holds together sister chromatids of replicated DNA

Question 13

What are condensins? What does each type do?

Answer 13

Ring shaped SMC protein complex that compacts duplicated chromosomes for segregation by forming loops and loops within loops.

Condensin II: replace interphase cohesins and forms larger loops when mitosis begins

Condensin I: forms loops within the loops made by condensin I

Question 14

What are ways DNA becomes accessible?

Answer 14

Chromatin remodeling complexes pull on DNA to loosen its grip to hide or expose a sequence of DNA

Histone modifying enzymes add acetyl, phosphate or methyl as docing sites for regulatory proteins that condense or expand chromatin.

Question 15

What are examples of modifying a histone?

Answer 15

1. Lysine (K) 9 trimethylation: closed chromatin, no gene expression
2. Lysine (K) 4 trimethylation + Lysine (K) 9 acetylation: gene expression

Question 16

What is the difference between heterochromatin and euchromatin?

Answer 16

Heterochromatin: condensed chromatin made of 40% interphase chromosome, with some permanently condensed or silenced regions.

Euchromatin: open chromatin where some regions are more condensed than others, depending on activity of cell

Question 17

How does heterochromatin spread to neighbouring regions of DNA? What’s an example?

Answer 17

Histone tail modification attract heterochromatin specific proteins and extends the region until it encounters a barrier DNA sequence. (e.g. acetyl group on lysine 9 blocks propagation of methylation and prevent spread of heterochromatin.)

Question 18

What is an example of disease caused by inappropriate packaging of genes?

Answer 18

Beta-globin that forms hemoglobin molecule is situated near heterochromatin. If a barrier sequence is deleted, heterochromatin will spread and deactivate beta-globin gene and cause severe anemia.

Question 19

What are barr bodies and why do they exist?

Answer 19

Discrete mass of chromatin inactivating a female’s second X chromosome to avoid the synthesis of twice the amount of mRNA.