TY - JOUR
T1 - Diversity among POU transcription factors in chromatin recognition and cell fate reprogramming
AU - Malik, Vikas
AU - Zimmer, Dennis
AU - Jauch, Ralf
N1 - Publisher Copyright:
© 2018, Springer International Publishing AG, part of Springer Nature.
PY - 2018/5/1
Y1 - 2018/5/1
N2 - The POU (Pit-Oct-Unc) protein family is an evolutionary ancient group of transcription factors (TFs) that bind specific DNA sequences to direct gene expression programs. The fundamental importance of POU TFs to orchestrate embryonic development and to direct cellular fate decisions is well established, but the molecular basis for this activity is insufficiently understood. POU TFs possess a bipartite ‘two-in-one’ DNA binding domain consisting of two independently folding structural units connected by a poorly conserved and flexible linker. Therefore, they represent a paradigmatic example to study the molecular basis for the functional versatility of TFs. Their modular architecture endows POU TFs with the capacity to accommodate alternative composite DNA sequences by adopting different quaternary structures. Moreover, associations with partner proteins crucially influence the selection of their DNA binding sites. The plentitude of DNA binding modes confers the ability to POU TFs to regulate distinct genes in the context of different cellular environments. Likewise, different binding modes of POU proteins to DNA could trigger alternative regulatory responses in the context of different genomic locations of the same cell. Prominent POU TFs such as Oct4, Brn2, Oct6 and Brn4 are not only essential regulators of development but have also been successfully employed to reprogram somatic cells to pluripotency and neural lineages. Here we review biochemical, structural, genomic and cellular reprogramming studies to examine how the ability of POU TFs to select regulatory DNA, alone or with partner factors, is tied to their capacity to epigenetically remodel chromatin and drive specific regulatory programs that give cells their identities.
AB - The POU (Pit-Oct-Unc) protein family is an evolutionary ancient group of transcription factors (TFs) that bind specific DNA sequences to direct gene expression programs. The fundamental importance of POU TFs to orchestrate embryonic development and to direct cellular fate decisions is well established, but the molecular basis for this activity is insufficiently understood. POU TFs possess a bipartite ‘two-in-one’ DNA binding domain consisting of two independently folding structural units connected by a poorly conserved and flexible linker. Therefore, they represent a paradigmatic example to study the molecular basis for the functional versatility of TFs. Their modular architecture endows POU TFs with the capacity to accommodate alternative composite DNA sequences by adopting different quaternary structures. Moreover, associations with partner proteins crucially influence the selection of their DNA binding sites. The plentitude of DNA binding modes confers the ability to POU TFs to regulate distinct genes in the context of different cellular environments. Likewise, different binding modes of POU proteins to DNA could trigger alternative regulatory responses in the context of different genomic locations of the same cell. Prominent POU TFs such as Oct4, Brn2, Oct6 and Brn4 are not only essential regulators of development but have also been successfully employed to reprogram somatic cells to pluripotency and neural lineages. Here we review biochemical, structural, genomic and cellular reprogramming studies to examine how the ability of POU TFs to select regulatory DNA, alone or with partner factors, is tied to their capacity to epigenetically remodel chromatin and drive specific regulatory programs that give cells their identities.
KW - Cellular reprogramming
KW - POU
KW - Pioneer TFs
KW - Transcriptional regulation
UR - http://www.scopus.com/inward/record.url?scp=85041346358&partnerID=8YFLogxK
U2 - 10.1007/s00018-018-2748-5
DO - 10.1007/s00018-018-2748-5
M3 - Review article
C2 - 29335749
AN - SCOPUS:85041346358
SN - 1420-682X
VL - 75
SP - 1587
EP - 1612
JO - Cellular and Molecular Life Sciences
JF - Cellular and Molecular Life Sciences
IS - 9
ER -