BACKGROUND: Developmental processes, including neuronal differentiation, require precise regulation of transcription. The RE-1 silencing transcription factor (Rest), is often called a "master neuronal regulator" due to its large number of neural-specific targets. Rest recruits CoRest (Rcor) and Sin3 corepressor complexes to gene regulatory sequences. CoRest not only associates with Rest, but with other transcription regulators. In this study, we generated zebrafish rcor1 mutants using transcription activator-like effector nucleases (TALENS), to study its requisite role in repression of Rest target genes as well as Rest-independent Rcor1 developmental functions. RESULTS: While rcor1 mutants have a slight decrease in fitness, most survived and produced viable offspring. We examined expression levels of RE1-containing genes in maternal zygotic rcor1 (MZrcor1) mutants and found that Rcor1 is generally not required for the repression of Rest target genes at early stages. However, MZrcor1 mutants undergo more rapid neurogenesis compared to controls. We found that at gastrula stages, Rcor1 acts as a repressor of her gene family, but at later stages, her6 decreased in the MZrcor1 mutant. CONCLUSIONS: Based on these findings, the central role of CoRest1 in neurogenesis is likely due to a Rest-independent role rather than as a Rest corepressor.
BACKGROUND: Developmental processes, including neuronal differentiation, require precise regulation of transcription. The RE-1 silencing transcription factor (Rest), is often called a "master neuronal regulator" due to its large number of neural-specific targets. Rest recruits CoRest (Rcor) and Sin3 corepressor complexes to gene regulatory sequences. CoRest not only associates with Rest, but with other transcription regulators. In this study, we generated zebrafish rcor1 mutants using transcription activator-like effector nucleases (TALENS), to study its requisite role in repression of Rest target genes as well as Rest-independent Rcor1 developmental functions. RESULTS: While rcor1 mutants have a slight decrease in fitness, most survived and produced viable offspring. We examined expression levels of RE1-containing genes in maternal zygotic rcor1 (MZrcor1) mutants and found that Rcor1 is generally not required for the repression of Rest target genes at early stages. However, MZrcor1 mutants undergo more rapid neurogenesis compared to controls. We found that at gastrula stages, Rcor1 acts as a repressor of her gene family, but at later stages, her6 decreased in the MZrcor1 mutant. CONCLUSIONS: Based on these findings, the central role of CoRest1 in neurogenesis is likely due to a Rest-independent role rather than as a Rest corepressor.
Authors: Jochen E Welcker; Luis R Hernandez-Miranda; Florian E Paul; Shiqi Jia; Andranik Ivanov; Matthias Selbach; Carmen Birchmeier Journal: Development Date: 2013-11-13 Impact factor: 6.868
Authors: Ahmad M Khalil; Mitchell Guttman; Maite Huarte; Manuel Garber; Arjun Raj; Dianali Rivea Morales; Kelly Thomas; Aviva Presser; Bradley E Bernstein; Alexander van Oudenaarden; Aviv Regev; Eric S Lander; John L Rinn Journal: Proc Natl Acad Sci U S A Date: 2009-07-01 Impact factor: 11.205
Authors: Jay H Kalin; Muzhou Wu; Andrea V Gomez; Yun Song; Jayanta Das; Dawn Hayward; Nkosi Adejola; Mingxuan Wu; Izabela Panova; Hye Jin Chung; Edward Kim; Holly J Roberts; Justin M Roberts; Polina Prusevich; Jeliazko R Jeliazkov; Shourya S Roy Burman; Louise Fairall; Charles Milano; Abdulkerim Eroglu; Charlotte M Proby; Albena T Dinkova-Kostova; Wayne W Hancock; Jeffrey J Gray; James E Bradner; Sergio Valente; Antonello Mai; Nicole M Anders; Michelle A Rudek; Yong Hu; Byungwoo Ryu; John W R Schwabe; Andrea Mattevi; Rhoda M Alani; Philip A Cole Journal: Nat Commun Date: 2018-01-04 Impact factor: 14.919