이 논문을 보고 느낀게 아직 논문들이 글로벌한 패턴을 볼 수 밖에 없다는 것을 느꼈다. 같은 component 가지고 시간과 상황에 따라 다른 역할을 해버리니 각각의 position 별로 시간에 따라 정확한 기능을 알지 못한다면 잘못된 해석만이 나올 뿐이다. 그런데 이 시간과 포지션 별로의 데이터 양이 얼마나 될까? 인간 게놈이 30억인데 내 기억으로 하나의 히스톤에 감기는 dna의 길이가 백오십 베이스 정도였던거 같은데.. 물론 링커도 있지만 그렇다면 수많은 갰수의 hisone이 나오게 되고 hisone의 종류도 기본 3가지 뿐 아니라 사이드도 있고 게다가 modification도 phosphorylation과 mono-에서 tri-까지의 methylation과 histone 하나에서도 아미노산 하나하나의 modification이 가능하게 되면.. 음.. 모든 경우에 수는 우주의 원자 수보다도 많게 되는게 아닐까 (얼마전 읽은 책에서 보니까 원자수가 생각보다 적었던 걸로 기억, 물론 말도 안될 수 있지만)..
그렇다고 해석하는데 포기할수 는 없지만.. 가히 포기 하고 싶어진다.
epigenetic code (histone modification) :
revealing a nuanced and intriguing language, not
a strict code, as the basis for transcriptional regulation through
the chromatin signaling pathway
1. acetylation of histone:
A well-characterized
posttranslational modification regulating chromatin
structure is the acetylation of histone N-terminal tails, which is
thought to facilitate transcriptional activation either by charge
neutralization of the tails’ interaction with DNA or by forming
a binding site for bromodomain-containing transcription factors, some of which can remodel nucleosomes
2. methylation of H3K4:
a modification generally associated with transcriptionally
active genes and a binding site for a variety of factors that include
histone-modifying and -remodeling activities
histone crosstalk: effect of prior nearby histone modification to subsequent histone modification
examples : first picture,
point mutation in H3K14 (acetylation site) results in the specific loss of H3K4 trimethylation.
phosphorylation of H3S10 interferes with binding of HP1 (heterochromatin protein 1) to methylated H3K9
reason : histone modification enzymes are constituted with multisubunit complex
example of histone crosstalk is the stimulation of
acetyltransferase activity of GCN5 toward the histone H3 tail by prior phosphorylation
(P) of serine 10. Acetylation, Ac.
understanding the activities of these histone modification crosstalk is not simple, because the transcriptional readout depends on context and timing. Second figure represent this characteristics.In A, show that depending on position and timing of binding of 14-3-3, a phosphoserine binding protein, to H3S10 it works differently. In B say that artificially increasing acetylation doesn't lead to productive trascription.
there is an example (fruit fly's dosage compensation study) which have different order of implementation of proteins.
