Opposing LSD1 complexes function in developmental gene activation and repression programmes

  title={Opposing LSD1 complexes function in developmental gene activation and repression programmes},
  author={Jianxun Wang and Kathleen M. Scully and Xiaoyan Zhu and Ling Cai and Jie Zhang and Gratien G. Prefontaine and Anna Krones and Kenneth a. Ohgi and Ping Zhu and Ivan Garcia-Bassets and Forrest Liu and Havilah Taylor and Jean Lozach and Friederike L Jayes and Kenneth S. Korach and Christopher K. Glass and Xiang-Dong Fu and Michael G. Rosenfeld},
Precise control of transcriptional programmes underlying metazoan development is modulated by enzymatically active co-regulatory complexes, coupled with epigenetic strategies. One thing that remains unclear is how specific members of histone modification enzyme families, such as histone methyltransferases and demethylases, are used in vivo to simultaneously orchestrate distinct developmental gene activation and repression programmes. Here, we report that the histone lysine demethylase, LSD1—a… 

Control of developmentally primed erythroid genes by combinatorial co-repressor actions

It is shown that the key haematopoietic LIM-domain-binding protein-1 (LDB1) TF complex contains several activator and repressor components that together maintain an erythroid-specific gene expression programme primed for rapid activation until differentiation is induced.

Pathological LSD1 mutations repress enhancer-mediated gene regulatory networks in early differentiation

Overall decreases in TF target gene expression during early lineage differentiation of LSD1 mutant stem cells, likely caused by increased activity of repressive histone deacetylases (HDACs), co-factors of LSD 1.

Drosophila LSD1‐CoREST demethylase complex regulates DPP/TGFβ signaling during wing development

It is found that the activity of a specific class of histone demethylation enzymes is required for the specification of vein cell fates during Drosophila wing development and that LSD1‐CoREST functions through control of rhomboid expression in an EGFR‐independent pathway.

Notch Represses Transcription by PRC2 Recruitment to the Ternary Complex

It is demonstrated that p19Arf and Klf4 are transcriptionally repressed in a Notch-dependent manner and the targeting of epigenetic enzymes to inhibit Notch activity or use in combinatorial therapy to provide a more profound therapeutic response is provided.

Enhancer decommissioning by LSD1 during embryonic stem cell differentiation

It is proposed that the LSD1–NuRD complex decommissions enhancers of the pluripotency program during differentiation, which is essential for the complete shutdown of the ESC gene expression program and the transition to new cell states.

Lsd1 interacts with cMyb to demethylate repressive histone marks and maintain inner ear progenitor identity

It is suggested that Lsd1-cMyb acts as a co-activator complex that maintains a regulatory module at the top of the inner ear gene network that maintains progenitor identity in the developing ear prior to lineage commitment.

Roles and regulation of histone methylation in animal development

It has been revealed that methylation and demethylation of both activating and repressive marks are essential for establishing embryonic and extra-embryonic lineages, for ensuring gene dosage compensation via genomic imprinting and for establishing body patterning via HOX gene regulation.

Sumoylation strategies in regulated repression by nuclear receptors and in function of tumor metastasis suppressor genes

The down-regulation of KAI1, a metastasis suppressor gene, in prostate cancer cells involved the inhibitory function of a [Beta]-catenin -Reptin complex, which required both induced catenin expression and recruitment of HDAC1 by Reptin, and which appears to play dual roles in transcriptional regulation in a context-dependent manner.



Coordinated histone modifications mediated by a CtBP co-repressor complex

The identification of a CtBP complex that contains the essential components for both gene targeting and coordinated histone modifications, allowing for the effective repression of genes targeted by CtBP is reported.

LSD1 demethylates repressive histone marks to promote androgen-receptor-dependent transcription

It is shown that lysine-specific demethylase 1 co-localizes with the androgen receptor in normal human prostate and prostate tumour and pargyline is identified as an inhibitor of LSD1, providing a mechanism by which demethylases control specific gene expression.

RBP-Jκ/SHARP Recruits CtIP/CtBP Corepressors To Silence Notch Target Genes

It is functionally demonstrate that the SHARP repression domain is necessary and sufficient to repress transcription and that the absence of this domain causes a dominant negative Notch-like phenotype.

CoREST: a functional corepressor required for regulation of neural-specific gene expression.

It is shown that CoREST, a newly identified human protein, functions as a corepressor for REST, a structural feature of the nuclear receptor and silencing mediator for retinoid and thyroid human receptors (SMRT)-extended corepressors that mediate inducible repression by steroid hormone receptors.

Corepressor-Dependent Silencing of Chromosomal Regions Encoding Neuronal Genes

The zinc-finger gene-specific repressor element RE-1 silencing transcription factor/neuronal restricted silencing factor (REST/NRSF) can mediate extraneuronal restriction by imposing either active repression via histone deacetylase recruitment or long-term gene silencing using a distinct functional complex.

Pc2-mediated Sumoylation of Smad-interacting Protein 1 Attenuates Transcriptional Repression of E-cadherin*

It is shown in vivo and in vitro that SIP1 is covalently modified by sumoylation at two conserved sites, Lys391 and Lys866, which may represent an important intervention target to modulate EMT in tumorigenesis.

A core–BRAF35 complex containing histone deacetylase mediates repression of neuronal-specific genes

It is shown that BHC mediates repression of neuron-specific genes through the cis-regulatory element known as the repressor element 1 or neural restrictive silencer (RE1/NRS).

Controlling nuclear receptors: the circular logic of cofactor cycles

This work has provided insights into the molecular mechanisms that are required to switch between repression and activation functions, the combinatorial roles of the multiple cofactor complexes that are necessary for mediating transcriptional regulation, and the central question of how several different signalling pathways can be integrated at the nuclear level to achieve specific profiles of gene expression.

ZEB represses transcription through interaction with the corepressor CtBP.

  • A. PostigoD. Dean
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1999
It is demonstrated that ZEB and zfh-1 interact with the corepressor CtBP to repress transcription and that the interaction of CtBP with ZEB at the promoter is necessary for repressor activity.