TOBF1 modulates mouse embryonic stem cell fate through regulating alternative splicing of pluripotency genes
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TOBF1 modulates mouse embryonic stem cell fate through regulating alternative splicing of pluripotency genes. / Aich, Meghali; Ansari, Asgar Hussain; Ding, Li; Iesmantavicius, Vytautas; Paul, Deepanjan; Choudhary, Chunaram; Maiti, Souvik; Buchholz, Frank; Chakraborty, Debojyoti.
In: Cell Reports, Vol. 42, No. 10, 113177, 2023.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - TOBF1 modulates mouse embryonic stem cell fate through regulating alternative splicing of pluripotency genes
AU - Aich, Meghali
AU - Ansari, Asgar Hussain
AU - Ding, Li
AU - Iesmantavicius, Vytautas
AU - Paul, Deepanjan
AU - Choudhary, Chunaram
AU - Maiti, Souvik
AU - Buchholz, Frank
AU - Chakraborty, Debojyoti
N1 - Publisher Copyright: © 2023 The Authors
PY - 2023
Y1 - 2023
N2 - Embryonic stem cells (ESCs) can undergo lineage-specific differentiation, giving rise to different cell types that constitute an organism. Although roles of transcription factors and chromatin modifiers in these cells have been described, how the alternative splicing (AS) machinery regulates their expression has not been sufficiently explored. Here, we show that the long non-coding RNA (lncRNA)-associated protein TOBF1 modulates the AS of transcripts necessary for maintaining stem cell identity in mouse ESCs. Among the genes affected is serine/arginine splicing factor 1 (SRSF1), whose AS leads to global changes in splicing and expression of a large number of downstream genes involved in the maintenance of ESC pluripotency. By overlaying information derived from TOBF1 chromatin occupancy, the distribution of its pluripotency-associated OCT-SOX binding motifs, and transcripts undergoing differential expression and AS upon its knockout, we describe local nuclear territories where these distinct events converge. Collectively, these contribute to the maintenance of mouse ESC identity.
AB - Embryonic stem cells (ESCs) can undergo lineage-specific differentiation, giving rise to different cell types that constitute an organism. Although roles of transcription factors and chromatin modifiers in these cells have been described, how the alternative splicing (AS) machinery regulates their expression has not been sufficiently explored. Here, we show that the long non-coding RNA (lncRNA)-associated protein TOBF1 modulates the AS of transcripts necessary for maintaining stem cell identity in mouse ESCs. Among the genes affected is serine/arginine splicing factor 1 (SRSF1), whose AS leads to global changes in splicing and expression of a large number of downstream genes involved in the maintenance of ESC pluripotency. By overlaying information derived from TOBF1 chromatin occupancy, the distribution of its pluripotency-associated OCT-SOX binding motifs, and transcripts undergoing differential expression and AS upon its knockout, we describe local nuclear territories where these distinct events converge. Collectively, these contribute to the maintenance of mouse ESC identity.
KW - alternative splicing
KW - CP: Stem cell research
KW - CRISPR interference
KW - mESCs
KW - OCT-SOX
KW - Panct1
KW - pluripotency
KW - SRSF1
KW - TOBF1
U2 - 10.1016/j.celrep.2023.113177
DO - 10.1016/j.celrep.2023.113177
M3 - Journal article
C2 - 37751355
AN - SCOPUS:85171970901
VL - 42
JO - Cell Reports
JF - Cell Reports
SN - 2211-1247
IS - 10
M1 - 113177
ER -
ID: 369122589