Inhibition of JAK2 activity lowers both the expression of the hematopoietic oncogene LMO2 and the phosphorylation of H3Y41 at its promoter in leukemic cells while enhancing HP1 binding at the same location.
[3] The ability to be transcribed is directly influenced by the degree of chromatin compaction at distinct chromosomal locations.
Non-coding repetitive DNA associated with specific chromosomal locations, such as centromeres and telomeres, is referred to as constitutive heterochromatin.
H3Y41p is closely controlled throughout the cell cycle, with phosphorylation occurring in M-phase and lasting until mid-S-phase; this happens before the septation index peaks, and its presence coincides with Swi6 displacement from centromeric heterochromatin.
[4] H3Y41p causes a transition in CD proteins, with Swi6/HP1 being displaced to provide RNA polymerase II access to the DNA and Chp1, a RITS component, being recruited for the RNAi-mediated formation of heterochromatin.
Researchers choose proteins that are known to modify histones to test their effects on transcription, and found that the stress-induced kinase, MSK1, inhibits RNA synthesis.
Thus results suggested that the acetylation of histones can stimulate transcription by suppressing an inhibitory phosphorylation by a kinase as MSK1.
Because of the ease with which proteins can be phosphorylated and dephosphorylated, this type of modification is a flexible mechanism for cells to respond to external signals and environmental conditions.
Reversible phosphorylation results in a conformational change in the structure in many enzymes and receptors, causing them to become activated or deactivated.
[9] In prokaryotic proteins phosphorylation occurs on the serine, threonine, tyrosine, histidine or arginine or lysine residues.
[11] The current understanding and interpretation of histones comes from two large scale projects: ENCODE and the Epigenomic roadmap.
This led to chromatin states, which define genomic regions by grouping different proteins and/or histone modifications together.
ChIP-Seq can be used to identify and quantify various DNA fragments for different histone modifications along a genomic region.