MCB 010 Topic 6: Epigenetics

epigenetics

-changes to the genome that can be heritable (cell generations, not human generations)

-does not effect the sequence of nucleotides, but rather chemical modifications to DNA or proteins that bind or package DNA

-effect the state of the chromatin and gene expression causes different phenotypes

-environment can cause epigenetic changes

chromatin

DNA packaged around histone proteins

-unit= nucleosomes

-can be further packed into dense structures like 20nm fiber or heterochromatin

nucleosome

DNA wrapped around a protein structure of 8 histone proteins

chromatin structure

highly dynamic

-degree of packing at the single nucleosome level to the order of full chromosomes can vary

-Euchromatin

-Heterochromatin

euchromatin

-less dense and "open" chromatin

-allows room for proteins to initiate transcription

-high transcription activity

-genes are "on"

heterochromatin

densely packed and "closed" chromatin

-prevents proteins from initiating transcription

-low transcription activity

-genes are "off"

___________________ affect gene expression because they drive the formation of heterochromatin or euchromatin

Epigenetic marks

types of epigenetic marks

-histone marks

-DNA methylation

histone marks/modifications

-chemical modification to histone proteins that change the state of the chromatins

-can be modified to tighten or loosen chromatin, encouraging or repressing transcription

-tags are added to histones, not DNA

DNA methylation (reading)

highly methylated regions of CpG dinucleotides tend to repress transcription and they are compacted

-may be important for cancer and aging

-can be maintained between cell generations

X inactivation

-one of two X chromosomes (in a female) is randomly inactivated and remains coiled as a Barr body

-happens separately in individual cells during embryonic development

-all cells descended from each of the original cells will maintain the same pattern of X-inactivation

Barr body

A dense body formed from a deactivated X chromosome.

-most genes are "off" and not transcribed

X-inactivation can lead to...

mosaic phenotypes in females for X-linked traits

-ex: calico cats

cellular differentiation

the transition from a stem cell to a specialized non-dividing cell type

Chromatin Compaction During Differentiation

regions of heterochromatin form over genes that are not required in the cell type, resulting in patches of heterochromatin and euchromatin

epigenome

overall pattern of chromatin modifications possessed by each individual organism

developmental epigenetics

control of differential gene expression during development

Tagging

-each cell types uses the genome in a specific manner by tagging

-heritable from cell to cell within each cell type

-tagging changes the organization making some genes or regions more ore less accessible for transcription reading

-reversible/dynamic vs static DNA sequences

epigenetic tags are...

-chemical modifications

-dynamic (can be added and removed)

-heritable over mitosis

-impact of the environment

DNA methylation (lecture)

direct modification that does not change the DNA sequences that drives heterochromatin

-causes gene silencing

-on specific Cs, not all (must be on the 5' end)

writer

protein (enzyme) that adds histone modifications

eraser

enzyme that removes histone modifications

reader

proteins that read histone modifications and alter gene activity and protein production