Three distinct patterns of histone H3Y41 phosphorylation mark active genes
Mark A Dawson1, Samuel D Foster, Andrew J Bannister
1Gurdon Institute and Department of Pathology, Cambridge, UK.
Cell Reports
|September 25, 2012
Summary
The Janus kinase 2 (JAK2) pathway regulates gene transcription by phosphorylating histone H3. This study maps histone H3 tyrosine 41 phosphorylation (H3Y41ph) genome-wide, revealing its role at promoters and gene bodies in hematopoietic cells.
Area of Science:
- Molecular Biology
- Cell Signaling
- Epigenetics
Background:
- The Janus kinase 2 (JAK2) tyrosine kinase is a key mediator of cytokine signaling pathways.
- JAK2 influences gene transcription by phosphorylating histone H3 at tyrosine 41 (H3Y41ph) within the nucleus.
Purpose of the Study:
- To define the genome-wide distribution of H3Y41ph in human erythroid leukemia cells.
- To elucidate the regulatory roles of H3Y41ph in gene transcription.
Main Methods:
- Chromatin immunoprecipitation coupled to massively parallel DNA sequencing (ChIP-seq) was employed.
- Analysis focused on human erythroid leukemia cell lines.
Main Results:
- H3Y41ph was identified at three distinct genomic locations: active promoters (overlapping H3K4me3), distal cis-regulatory elements (coinciding with STAT5 binding), and transcribed regions of active hematopoietic genes.
- These findings highlight specific patterns of H3Y41ph localization.
Conclusions:
- H3Y41ph is a significant epigenetic mark involved in transcriptional regulation.
- This research provides insights into how extracellular signals are translated into coordinated transcriptional responses via the JAK2 pathway.
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