Many biological phenomena including health and disease can be traced to the proper or improper expression of a gene or genomic loci. Hence, knowledge of the molecular mechanisms that regulate genome expression is critical to understand a wide range of biological and biomedical topics. Exploiting natural genetic and organismic variation, genomics, and bioinformatics we thrive to greater our understanding of the fundamental molecular mechanisms that regulate the expression of genomes, especially from the perspective of the transcription start site (TSS). Capturing the transcription start site also provides a spatial anchor which revealed that many transcription factors (TFs), including canonical activators like NRF1, NFY, Sp1, activate or repress transcription initiation depending on their precise position relative to the TSS. As such, this spatial grammar of transcription factor function can collectively guide the site and frequency of transcription initiation. More broadly, this spatial grammar could explain how similar assortments of transcription factor binding sites (DNA motifs) can generate distinct gene regulatory outcomes depending on their spatial configuration, and underscore a critical role for transcription start site data in decoding the regulatory information of our genome.
Latest publications
- DNMT3A haploinsufficiency causes dichotomous DNA methylation defects at enhancers in mature human immune cells. Lim JY, Duttke SH, et al. Journal of Experimental Medicine. 2021, PMID: 33970190
- Identification and dynamic quantification of regulatory elements using total RNA. Duttke SH, et al. Genome Research. 2019, PMID: 31649059
- Analysis of Genetically Diverse Macrophages Reveals Local and Domain-wide Mechanisms that Control Transcription Factor Binding and Function. Link VM, Duttke SH, et al. Cell. 2018, PMID: 2977994