Learning Epigenetics from ShirleyLiu
1 Transcription Regulation & motif finding
from: https://www.youtube.com/watch?v=K2gKdFPipv0&feature=youtu.be&ab_channel=XiaoleShirleyLiu
TFs are proteins combine specific sequence and they usually recognize a sequnece motif or a pattern, which will regulate the nearby gene expression.
2 Epigenetics
from: https://www.youtube.com/watch?v=CnECsb6Eb2A&feature=youtu.be&ab_channel=XiaoleShirleyLiu
Hetitable changes in gene function that occurs without a change in the DNA sequence
- Nurture vs Nature
3.1 DNA Methylation
from: https://www.youtube.com/watch?v=OnCZlC0T2vs&feature=youtu.be&ab_channel=XiaoleShirleyLiu
- Detection using bisulfite sequencing:
- BS treatment => unmethyl C->T => sequence 30X
- High resolution, but expensive
3.2 DNA Methylation Function
DNA methylation controls gene expression
unmethylated C follow with G, usually becomes T-G (so there’s lots of T-G, C-A in genome)
many highly expressed genes have CpG methylation in gene body especially on exons
large unmethlylated cayon
- promoter unmethylated, more TFs really binding there
DNA methylation in cancer
cancer landmark: widespread hypomethylation and focal CpG island hypermethylation (maybe at the promoter of tumor supressor gene) [normal cell promoter is on, while in cancer cells is locked ]
Methylation variable regions in CpG island shores in cancer
DNA Demethylation
- Hydroxyl methylation (hmC) is an intermediate step between mC and C
- hmC enciched in TF binding sites (TFBS)
- Need TET family of proteins which is mutated in many cancers
4 Nucleosome position
- Most TFs like to bind the nucleosome-free DNA
- Only a minority of TFs can bind nucleosome DNA and they will squeeze out histone to make it open => “Pioneering TFs” (that means, they have to go there first to open that region then let other TFs come in)
MNase-seq：Micrococcal nuclease. MNase digestion of chromatin was key to early studies of chromatin structure
