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

image-20201029112929723

  • Nurture vs Nature
  • image-20201029123344241

3.1 DNA Methylation

from: https://www.youtube.com/watch?v=OnCZlC0T2vs&feature=youtu.be&ab_channel=XiaoleShirleyLiu

image-20201029123725537

  • Detection using bisulfite sequencing:
    • BS treatment => unmethyl C->T => sequence 30X
    • High resolution, but expensive

3.2 DNA Methylation Function

from: https://youtu.be/RvSsFTUfGy4

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 image-20201029105918173

large unmethlylated cayon
  • promoter unmethylated, more TFs really binding there
  • image-20201029110404598

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 ]

    image-20201029103944811

  • Methylation variable regions in CpG island shores in cancer image-20201029111235598

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

image-20201029133646900

  • 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

Yunze Liu
Yunze Liu
Bioinformatics Sharer

Co-founder of Bioinfoplanet(生信星球)

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