RCOR2 Is a Subunit of the LSD1 Complex That Regulates ESC Property and Substitutes for SOX2 in Reprogramming Somatic Cells to Pluripotency

Yang, Peng; Wang, Yixuan; Chen, Jiayu; Li, Hong; Kang, Lan; Chen, She; Gao, Shaorong

doi:10.1002/stem.634

Cited by 82 publications

(97 citation statements)

References 52 publications

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“…LSD1 has also been found to maintain both the undifferentiated state and proliferative capacity of pluripotent cells, which express relatively high levels of LSD1 (Sun et al, 2010;Adamo et al, 2011;Yang et al, 2011;Nair et al, 2012). Here, we have identified a new transcription-independent role for LSD1 in the reestablishment of nuclear architecture following mitotic cell division.…”

Section: Discussionmentioning

confidence: 78%

The lysine demethylase LSD1 is required for nuclear envelope formation at the end of mitosis

Schooley

Moreno-Andrés

Magistris

et al. 2015

Journal of Cell Science

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The metazoan nucleus breaks down and reassembles during each cell division. Upon mitotic exit, the successful reestablishment of an interphase nucleus requires the coordinated reorganization of chromatin and formation of a functional nuclear envelope. Here, we report that the histone demethylase LSD1 (also known as KDM1A) plays a crucial role in nuclear assembly at the end of mitosis. Downregulation of LSD1 in cells extends telophase and impairs nuclear pore complex assembly. In vitro, LSD1 demethylase activity is required for the recruitment of MEL28 (also known as ELYS and AHCTF1) and nuclear envelope precursor vesicles to chromatin, crucial steps in nuclear reassembly. Accordingly, the formation of a closed nuclear envelope and nuclear pore complex assembly are impaired upon depletion of LSD1 or inhibition of its activity. Our results identify histone demethylation by LSD1 as a new regulatory mechanism linking the chromatin state and nuclear envelope formation at the end of mitosis.

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Section: Discussionmentioning

confidence: 78%

The lysine demethylase LSD1 is required for nuclear envelope formation at the end of mitosis

Schooley

Moreno-Andrés

Magistris

et al. 2015

Journal of Cell Science

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“…A recent study revealed that even though CoREST family members CoREST1, CoREST2 and CoREST3 co-purify LSD1 equally well, enzymatic activities of these complexes differ significantly. 77,78 Thus, association of LSD1 with CoREST3 leads to diminished catalytic activity, that can antagonize the histone demethylation activity of CoREST1 complexes. 77,79 Therefore, it is plausible that the balance between homologous CoREST complexes and the active exchange of CoREST subunits could be important in different scenarios of cellular differentiation.…”

Section: The Corest Proteinmentioning

confidence: 99%

“…77,79 Therefore, it is plausible that the balance between homologous CoREST complexes and the active exchange of CoREST subunits could be important in different scenarios of cellular differentiation. 78,79 Structural studies have provided insight into how some of the CoREST complex subunits interact with each other and their chromatin substrate. [80][81][82][83] Importantly, the LSD1 enzyme alone demethylates H3K4 within peptides or bulk histones in vitro.…”

Section: The Corest Proteinmentioning

confidence: 99%

Chromatin regulation: How complex does it get?

Meier¹,

Brehm

2014

Epigenetics

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“…Furthermore, RCOR2 is recruited by some of the same RCOR1-associated transcription factors, including REST, GFI1B, and ZMYND8 (15,16). Despite knowledge of their cell-specific roles in some contexts (2,17), the importance of RCOR1/2 in brain development has yet to be established definitively.…”

mentioning

confidence: 99%

REST corepressors RCOR1 and RCOR2 and the repressor INSM1 regulate the proliferation–differentiation balance in the developing brain

Monaghan

Nechiporuk

Jeng

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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The transcriptional events that lead to the cessation of neural proliferation, and therefore enable the production of proper numbers of differentiated neurons and glia, are still largely uncharacterized. Here, we report that the transcription factor Insulinoma-associated 1 (INSM1) forms complexes with RE1 Silencing Transcription factor (REST) corepressors RCOR1 and RCOR2 in progenitors in embryonic mouse brain. Mice lacking both RCOR1 and RCOR2 in developing brain die perinatally and generate an abnormally high number of neural progenitors at the expense of differentiated neurons and oligodendrocyte precursor cells. In addition, Rcor1/2 deletion detrimentally affects complex morphological processes such as closure of the interganglionic sulcus. We find that INSM1, a transcription factor that induces cell-cycle arrest, is coexpressed with RCOR1/2 in a subset of neural progenitors and forms complexes with RCOR1/2 in embryonic brain. Further, the Insm1 −/− mouse phenocopies predominant brain phenotypes of the Rcor1/2 knockout. A large number of genes are concordantly misregulated in both knockout genotypes, and a majority of the down-regulated genes are targets of REST. Rest transcripts are up-regulated in both knockouts, and reducing transcripts to control levels in the Rcor1/2 knockout partially rescues the defect in interganglionic sulcus closure. Our findings indicate that an INSM1/RCOR1/2 complex controls the balance of proliferation and differentiation during brain development.he development of the nervous system is an intricately orchestrated series of events beginning with formation of neuroepithelia. Progenitors that emerge from neuroepithelial stem cells undergo several proliferative transitions before ceasing to divide and terminally differentiating into neurons and glia. Both maintenance of the proliferative state and terminal transition to differentiated neurons and glia are regulated, in part, by chromatin-modifying proteins that are recruited to genes by specific transcription factors. In many cases, however, chromatin-modifying proteins have only been studied in vitro, and their roles in vivo remain unknown. For example, a protein whose importance in epigenetic regulation of neural genes has been recognized is RE1 Silencing Transcription factor (REST) Corepressor 1 (RCOR1) (1, reviewed in ref. 2). RCOR1 was identified originally as a direct binding partner for the master transcriptional regulator of neural genes, REST (3-5). The REST/RCOR1 complex has been studied primarily in cultured stem/progenitor cells, neurons, and glia (6-9). Like many other adaptor proteins in transcriptional complexes, RCOR1 does not have intrinsic enzymatic activity but rather binds directly to chromatin-modifying enzymes including histone deacetylases 1 and 2 (HDAC1/2) and the histone demethylase KDM1A (LSD1) (10-12). A related protein, RCOR2, shares ∼90% homology with RCOR1 in the ELM2 and SANT functional domains (13) and is also found in complexes with KDM1A and HDAC1/2 (14). Furthermore, RCOR2 is recruited by some of t...

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RCOR2 Is a Subunit of the LSD1 Complex That Regulates ESC Property and Substitutes for SOX2 in Reprogramming Somatic Cells to Pluripotency

Cited by 82 publications

References 52 publications

The lysine demethylase LSD1 is required for nuclear envelope formation at the end of mitosis

The lysine demethylase LSD1 is required for nuclear envelope formation at the end of mitosis

Chromatin regulation: How complex does it get?

REST corepressors RCOR1 and RCOR2 and the repressor INSM1 regulate the proliferation–differentiation balance in the developing brain

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