Discovery of widespread transcription initiation at microsatellites predictable by sequence-based deep neural network
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Discovery of widespread transcription initiation at microsatellites predictable by sequence-based deep neural network. / Grapotte, Mathys; Saraswat, Manu; Bessière, Chloé; Menichelli, Christophe; Ramilowski, Jordan A.; Severin, Jessica; Hayashizaki, Yoshihide; Itoh, Masayoshi; Tagami, Michihira; Murata, Mitsuyoshi; Kojima-Ishiyama, Miki; Noma, Shohei; Noguchi, Shuhei; Kasukawa, Takeya; Hasegawa, Akira; Suzuki, Harukazu; Nishiyori-Sueki, Hiromi; Frith, Martin C.; Abugessaisa, Imad; Aitken, Stuart; Aken, Bronwen L.; Alam, Intikhab; Alam, Tanvir; Alasiri, Rami; Alhendi, Ahmad M. N.; Alinejad-Rokny, Hamid; Alvarez, Mariano J.; Andersson, Robin; Arakawa, Takahiro; Araki, Marito; Arbel, Taly; Bornholdt, Jette; Boyd, Mette; Chen, Yun; Coskun, Mehmet; Dalby, Maria; Ienasescu, Hans; Jørgensen, Mette; Kaczkowski, Bogumil; Kere, Juha; Li, Kang; Lilje, Berit; Nepal, Chirag; Nguyen, Quan Hoang; Nielsen, Lars K.; Rennie, Sarah; Sandelin, Albin; Valen, Eivind; Vitezic, Morana; Vitting-Seerup, Kristoffer; FANTOM Consortium.
In: Nature Communications, Vol. 12, 3297, 2021.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Discovery of widespread transcription initiation at microsatellites predictable by sequence-based deep neural network
AU - Grapotte, Mathys
AU - Saraswat, Manu
AU - Bessière, Chloé
AU - Menichelli, Christophe
AU - Ramilowski, Jordan A.
AU - Severin, Jessica
AU - Hayashizaki, Yoshihide
AU - Itoh, Masayoshi
AU - Tagami, Michihira
AU - Murata, Mitsuyoshi
AU - Kojima-Ishiyama, Miki
AU - Noma, Shohei
AU - Noguchi, Shuhei
AU - Kasukawa, Takeya
AU - Hasegawa, Akira
AU - Suzuki, Harukazu
AU - Nishiyori-Sueki, Hiromi
AU - Frith, Martin C.
AU - Abugessaisa, Imad
AU - Aitken, Stuart
AU - Aken, Bronwen L.
AU - Alam, Intikhab
AU - Alam, Tanvir
AU - Alasiri, Rami
AU - Alhendi, Ahmad M. N.
AU - Alinejad-Rokny, Hamid
AU - Alvarez, Mariano J.
AU - Andersson, Robin
AU - Arakawa, Takahiro
AU - Araki, Marito
AU - Arbel, Taly
AU - Bornholdt, Jette
AU - Boyd, Mette
AU - Chen, Yun
AU - Coskun, Mehmet
AU - Dalby, Maria
AU - Ienasescu, Hans
AU - Jørgensen, Mette
AU - Kaczkowski, Bogumil
AU - Kere, Juha
AU - Li, Kang
AU - Lilje, Berit
AU - Nepal, Chirag
AU - Nguyen, Quan Hoang
AU - Nielsen, Lars K.
AU - Rennie, Sarah
AU - Sandelin, Albin
AU - Valen, Eivind
AU - Vitezic, Morana
AU - Vitting-Seerup, Kristoffer
AU - FANTOM Consortium
N1 - Author correction: https://www.nature.com/articles/s41467-022-28758-y
PY - 2021
Y1 - 2021
N2 - Using the Cap Analysis of Gene Expression (CAGE) technology, the FANTOM5 consortium provided one of the most comprehensive maps of transcription start sites (TSSs) in several species. Strikingly, ~72% of them could not be assigned to a specific gene and initiate at unconventional regions, outside promoters or enhancers. Here, we probe these unassigned TSSs and show that, in all species studied, a significant fraction of CAGE peaks initiate at microsatellites, also called short tandem repeats (STRs). To confirm this transcription, we develop Cap Trap RNA-seq, a technology which combines cap trapping and long read MinION sequencing. We train sequence-based deep learning models able to predict CAGE signal at STRs with high accuracy. These models unveil the importance of STR surrounding sequences not only to distinguish STR classes, but also to predict the level of transcription initiation. Importantly, genetic variants linked to human diseases are preferentially found at STRs with high transcription initiation level, supporting the biological and clinical relevance of transcription initiation at STRs. Together, our results extend the repertoire of non-coding transcription associated with DNA tandem repeats and complexify STR polymorphism.
AB - Using the Cap Analysis of Gene Expression (CAGE) technology, the FANTOM5 consortium provided one of the most comprehensive maps of transcription start sites (TSSs) in several species. Strikingly, ~72% of them could not be assigned to a specific gene and initiate at unconventional regions, outside promoters or enhancers. Here, we probe these unassigned TSSs and show that, in all species studied, a significant fraction of CAGE peaks initiate at microsatellites, also called short tandem repeats (STRs). To confirm this transcription, we develop Cap Trap RNA-seq, a technology which combines cap trapping and long read MinION sequencing. We train sequence-based deep learning models able to predict CAGE signal at STRs with high accuracy. These models unveil the importance of STR surrounding sequences not only to distinguish STR classes, but also to predict the level of transcription initiation. Importantly, genetic variants linked to human diseases are preferentially found at STRs with high transcription initiation level, supporting the biological and clinical relevance of transcription initiation at STRs. Together, our results extend the repertoire of non-coding transcription associated with DNA tandem repeats and complexify STR polymorphism.
U2 - 10.1038/s41467-021-23143-7
DO - 10.1038/s41467-021-23143-7
M3 - Journal article
C2 - 34078885
AN - SCOPUS:85107388625
VL - 12
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 3297
ER -
ID: 276159194