SwePub - sökning: id:"swepub:oai:DiVA.org:liu-15...

Numrering	Referens	Omslagsbild	Hitta
1.	Fonseca, Gregory J, et al. (författare) Diverse motif ensembles specify non-redundant DNA binding activities of AP-1 family members in macrophages. 2019 Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1 Tidskriftsartikel (refereegranskat)abstract Mechanisms by which members of the AP-1 family of transcription factors play non-redundant biological roles despite recognizing the same DNA sequence remain poorly understood. To address this question, here we investigate the molecular functions and genome-wide DNA binding patterns of AP-1 family members in primary and immortalized mouse macrophages. ChIP-sequencing shows overlapping and distinct binding profiles for each factor that were remodeled following TLR4 ligation. Development of a machine learning approach that jointly weighs hundreds of DNA recognition elements yields dozens of motifs predicted to drive factor-specific binding profiles. Machine learning-based predictions are confirmed by analysis of the effects of mutations in genetically diverse mice and by loss of function experiments. These findings provide evidence that non-redundant genomic locations of different AP-1 family members in macrophages largely result from collaborative interactions with diverse, locus-specific ensembles of transcription factors and suggest a general mechanism for encoding functional specificities of their common recognition motif.

Fonseca, Gregory J, et al. (författare)
Diverse motif ensembles specify non-redundant DNA binding activities of AP-1 family members in macrophages.
2019
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1
Tidskriftsartikel (refereegranskat)abstract
- Mechanisms by which members of the AP-1 family of transcription factors play non-redundant biological roles despite recognizing the same DNA sequence remain poorly understood. To address this question, here we investigate the molecular functions and genome-wide DNA binding patterns of AP-1 family members in primary and immortalized mouse macrophages. ChIP-sequencing shows overlapping and distinct binding profiles for each factor that were remodeled following TLR4 ligation. Development of a machine learning approach that jointly weighs hundreds of DNA recognition elements yields dozens of motifs predicted to drive factor-specific binding profiles. Machine learning-based predictions are confirmed by analysis of the effects of mutations in genetically diverse mice and by loss of function experiments. These findings provide evidence that non-redundant genomic locations of different AP-1 family members in macrophages largely result from collaborative interactions with diverse, locus-specific ensembles of transcription factors and suggest a general mechanism for encoding functional specificities of their common recognition motif.

Träfflista för sökning "id:"swepub:oai:DiVA.org:liu-154612" "