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Sequence determinantsof human generegulatory elements Biswajyoti SahuTuomo HartonenPäivi Pihlajamaa2022 год

Sequence determinants of human gene regulatory elements
статья из журнала

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Аннотация: Abstract DNA can determine where and when genes are expressed, but the full set of sequence determinants that control gene expression is unknown. Here, we measured the transcriptional activity of DNA sequences that represent an ~100 times larger sequence space than the human genome using massively parallel reporter assays (MPRAs). Machine learning models revealed that transcription factors (TFs) generally act in an additive manner with weak grammar and that most enhancers increase expression from a promoter by a mechanism that does not appear to involve specific TF–TF interactions. The enhancers themselves can be classified into three types: classical, closed chromatin and chromatin dependent. We also show that few TFs are strongly active in a cell, with most activities being similar between cell types. Individual TFs can have multiple gene regulatory activities, including chromatin opening and enhancing, promoting and determining transcription start site (TSS) activity, consistent with the view that the TF binding motif is the key atomic unit of gene expression.
Год издания: 2022
Авторы: Biswajyoti Sahu, Tuomo Hartonen, Päivi Pihlajamaa, Bei Wei, Kashyap Dave, Fangjie Zhu, Eevi Kaasinen, Katja Lidschreiber, Michael Lidschreiber, Carsten O. Daub, Patrick Cramer, Teemu Kivioja, Jussi Taipale
Издательство: Nature Portfolio
Источник: Nature Genetics
Ключевые слова: Genomics and Chromatin Dynamics, RNA and protein synthesis mechanisms, RNA Research and Splicing
Другие ссылки: Nature Genetics (PDF)
Nature Genetics (HTML)
GoeScholar The Publication Server of the Georg-August-Universität Göttingen (Georg-August-Universität Göttingen) (PDF)
GoeScholar The Publication Server of the Georg-August-Universität Göttingen (Georg-August-Universität Göttingen) (HTML)
PubMed Central (HTML)
Apollo (University of Cambridge) (PDF)
Apollo (University of Cambridge) (HTML)
bioRxiv (Cold Spring Harbor Laboratory) (HTML)
PubMed (HTML)