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Biology subjects

Tenen, D. E.

Publications and source records attributed to Tenen, D. E..

2 recordsLinked to original sources

ChIP-AP, An Integrated ChIP-Seq Analysis Pipeline

ChIP-Seq is a technique used to analyse protein-DNA interactions. The protein-DNA complex is pulled down using a protein antibody, after which sequencing and analysis of the bound DNA fragments is performed. A key bioinformatics analysis step is "peak" calling - identifying regions of enrichment. Benchmarking studies have consistently shown that no optimal peak caller exists. Peak callers have distinct selectivity and specificity characteristics which are often not additive and seldom completely overlap in many scenarios. In the absence of a universal peak caller, we rationalized one ought to utilize multiple peak-callers to 1) gauge peak confidence as determined through detection by multiple algorithms, and 2) more thoroughly survey the protein-bound landscape by capturing peaks not detected by individual peak callers owing to algorithmic limitations and biases. We therefore developed an integrated ChIP-Seq Analysis Pipeline (ChIP-AP) which performs all analysis steps from raw fastq files to final result, and utilizes four commonly used peak callers to more thoroughly and comprehensively analyse datasets. Results are integrated and presented in a single file enabling users to apply selectivity and sensitivity thresholds to select the consensus peak set, the union peak set, or any sub-set in-between to more confidently and comprehensively explore the protein-bound landscape. (https://github.com/JSuryatenggara/ChIP-AP).

bioinformatics↗

Myeloid lncRNA LOUP Mediates Opposing Regulatory Effects of RUNX1 and RUNX1-ETO in t(8;21) AML

The mechanism underlying cell type-specific gene induction conferred by ubiquitous transcription factors as well as disruptions caused by their chimeric derivatives in leukemia is not well understood. Here we investigate whether RNAs coordinate with transcription factors to drive myeloid gene transcription. In an integrated genome-wide approach surveying for gene loci exhibiting concurrent RNA- and DNA-interactions with the broadly expressed transcription factor RUNX1, we identified the long noncoding RNA LOUP. This myeloid-specific and polyadenylated lncRNA induces myeloid differentiation and inhibits cell growth, acting as a transcriptional inducer of the myeloid master regulator PU.1. Mechanistically, LOUP recruits RUNX1 to both the PU.1 enhancer and the promoter, leading to the formation of an active chromatin loop. In t(8;21) acute myeloid leukemia, wherein RUNX1 is fused to ETO, the resulting oncogenic fusion protein RUNX1-ETO limits chromatin accessibility at the LOUP locus, causing inhibition of LOUP and PU.1 expression. These findings highlight the important role of the interplay between cell type-specific RNAs and transcription factors as well as their oncogenic derivatives in modulating lineage-gene activation and raise the possibility that RNA regulators of transcription factors represent alternative targets for therapeutic development. KEY POINTSO_LIlncRNA LOUP coordinates with RUNX1 to induces PU.1 long-range transcription, conferring myeloid differentiation and inhibiting cell growth. C_LIO_LIRUNX1-ETO limits chromatin accessibility at the LOUP locus, causing inhibition of LOUP and PU.1 expression in t(8;21) AML. C_LI

cancer biology↗