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Promoter Capture Hi-C: High-resolution, Genome-wide Profiling of Promoter Interactions
Published on: June 28, 2018
Structurally differentiated cis-elements that interact with PU.1 are functionally distinguishable in acute
Maoxiang Qian1, Wen Jin, Xuehua Zhu
1Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences CAS, Shanghai 200025, China.
Journal of Hematology & Oncology
|April 4, 2013
Summary
This study defines PU.1 binding sites in acute promyelocytic leukemia (APL) cells, revealing distinct cis-element types. These elements, particularly those interacting with PML/RARα, are crucial in oncogenesis and acute myeloid leukemia (AML) pathogenesis.
Area of Science:
- Molecular Biology
- Genomics
- Cancer Research
Background:
- Transcription factor PU.1 is a key regulator of myeloid differentiation, and its disruption is linked to acute myeloid leukemia (AML).
- Understanding PU.1's cis-elements at a whole-genome level is crucial for comprehending its role in both normal and malignant hematopoiesis.
Purpose of the Study:
- To map the genome-wide binding sites (cistrome) of PU.1 in acute promyelocytic leukemia (APL) cells.
- To characterize the cis-regulatory elements that interact with PU.1 in the context of APL.
Main Methods:
- Chromatin immunoprecipitation followed by deep sequencing (ChIP-seq) to identify in vivo PU.1 binding sites across the genome.
- ChIP-quantitative PCR and luciferase reporter assays for validation of binding events and transcriptional activity.
- Computational analyses including motif mining, evolutionary conservation, and functional enrichment to characterize cis-elements.
Main Results:
- Identified 26,907 significantly enriched PU.1 binding regions in NB4 APL cells.
- PU.1 functions as a dual promoter-enhancer binding factor, interacting with two distinct motif types: a long, high-affinity motif in distal regions and a short, evolutionarily constrained motif in proximal regions.
- The short PU.1 motif preferentially co-occurs with other factors, notably PML/RARα, and genes co-targeted by PU.1 and PML/RARα are implicated in oncogenesis and AML pathogenesis.
Conclusions:
- Structurally distinct cis-elements interacting with PU.1 exhibit functional differences in APL.
- The sequence diversity of PU.1 cis-elements is a critical mechanism for interpreting genomic information and contributing to distinct cellular functions in physiological and pathological states.
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