A Non-canonical BCOR-PRC1.1 Complex Represses Differentiation Programs in Human ESCs

Zheng Wang, Micah D Gearhart, Yu Wei Lee, Ishan Kumar, Bulat Ramazanov, Yan Zhang, Charles Hernandez, Alice Y. Lu, Nils Neuenkirchen, Jingjing Deng, Jiaqi Jin, Yuval Kluger, Thomas A. Neubert, Vivian J Bardwell, Natalia B. Ivanova

Research output: Contribution to journalArticle

  • 1 Citations

Abstract

Polycomb group proteins regulate self-renewal and differentiation in many stem cell systems. When assembled into two canonical complexes, PRC1 and PRC2, they sequentially deposit H3K27me3 and H2AK119ub histone marks and establish repressive chromatin, referred to as Polycomb domains. Non-canonical PRC1 complexes retain RING1/RNF2 E3-ubiquitin ligases but have unique sets of accessory subunits. How these non-canonical complexes recognize and regulate their gene targets remains poorly understood. Here, we show that the BCL6 co-repressor (BCOR), a member of the PRC1.1 complex, is critical for maintaining primed pluripotency in human embryonic stem cells (ESCs). BCOR depletion leads to the erosion of Polycomb domains at key developmental loci and the initiation of differentiation along endoderm and mesoderm lineages. The C terminus of BCOR regulates the assembly and targeting of the PRC1.1 complex, while the N terminus contributes to BCOR-PRC1.1 repressor function. Our findings advance understanding of Polycomb targeting and repression in ESCs and could apply broadly across developmental systems. Molecular networks responsible for the maintenance of primed pluripotency in human embryonic stem cells (hESCs) remain poorly defined. Wang et al. identify BCOR as a critical hESC regulator that defines a subtype of the PRC1.1 complexes with distinct recruitment and repression mechanisms that are essential for silencing differentiation programs in hESCs.

LanguageEnglish (US)
Pages235-251.e9
JournalCell Stem Cell
Volume22
Issue number2
DOIs
StatePublished - Feb 1 2018

Fingerprint

Co-Repressor Proteins
Histone Code
Polycomb-Group Proteins
Endoderm
Ubiquitin-Protein Ligases
Mesoderm
Embryonic Stem Cells
Chromatin
Stem Cells
Maintenance
Human Embryonic Stem Cells
Genes

Keywords

  • BCOR
  • human embryonic stem cells
  • pluripotency
  • polycomb repressive complexes

PubMed: MeSH publication types

  • Journal Article

Cite this

Wang, Z., Gearhart, M. D., Lee, Y. W., Kumar, I., Ramazanov, B., Zhang, Y., ... Ivanova, N. B. (2018). A Non-canonical BCOR-PRC1.1 Complex Represses Differentiation Programs in Human ESCs. Cell Stem Cell, 22(2), 235-251.e9. https://doi.org/10.1016/j.stem.2017.12.002

A Non-canonical BCOR-PRC1.1 Complex Represses Differentiation Programs in Human ESCs. / Wang, Zheng; Gearhart, Micah D; Lee, Yu Wei; Kumar, Ishan; Ramazanov, Bulat; Zhang, Yan; Hernandez, Charles; Lu, Alice Y.; Neuenkirchen, Nils; Deng, Jingjing; Jin, Jiaqi; Kluger, Yuval; Neubert, Thomas A.; Bardwell, Vivian J; Ivanova, Natalia B.

In: Cell Stem Cell, Vol. 22, No. 2, 01.02.2018, p. 235-251.e9.

Research output: Contribution to journalArticle

Wang, Z, Gearhart, MD, Lee, YW, Kumar, I, Ramazanov, B, Zhang, Y, Hernandez, C, Lu, AY, Neuenkirchen, N, Deng, J, Jin, J, Kluger, Y, Neubert, TA, Bardwell, VJ & Ivanova, NB 2018, 'A Non-canonical BCOR-PRC1.1 Complex Represses Differentiation Programs in Human ESCs' Cell Stem Cell, vol. 22, no. 2, pp. 235-251.e9. https://doi.org/10.1016/j.stem.2017.12.002
Wang, Zheng ; Gearhart, Micah D ; Lee, Yu Wei ; Kumar, Ishan ; Ramazanov, Bulat ; Zhang, Yan ; Hernandez, Charles ; Lu, Alice Y. ; Neuenkirchen, Nils ; Deng, Jingjing ; Jin, Jiaqi ; Kluger, Yuval ; Neubert, Thomas A. ; Bardwell, Vivian J ; Ivanova, Natalia B. / A Non-canonical BCOR-PRC1.1 Complex Represses Differentiation Programs in Human ESCs. In: Cell Stem Cell. 2018 ; Vol. 22, No. 2. pp. 235-251.e9.
@article{0c39cb886d29451a9cf0434d4d7aac23,
title = "A Non-canonical BCOR-PRC1.1 Complex Represses Differentiation Programs in Human ESCs",
abstract = "Polycomb group proteins regulate self-renewal and differentiation in many stem cell systems. When assembled into two canonical complexes, PRC1 and PRC2, they sequentially deposit H3K27me3 and H2AK119ub histone marks and establish repressive chromatin, referred to as Polycomb domains. Non-canonical PRC1 complexes retain RING1/RNF2 E3-ubiquitin ligases but have unique sets of accessory subunits. How these non-canonical complexes recognize and regulate their gene targets remains poorly understood. Here, we show that the BCL6 co-repressor (BCOR), a member of the PRC1.1 complex, is critical for maintaining primed pluripotency in human embryonic stem cells (ESCs). BCOR depletion leads to the erosion of Polycomb domains at key developmental loci and the initiation of differentiation along endoderm and mesoderm lineages. The C terminus of BCOR regulates the assembly and targeting of the PRC1.1 complex, while the N terminus contributes to BCOR-PRC1.1 repressor function. Our findings advance understanding of Polycomb targeting and repression in ESCs and could apply broadly across developmental systems. Molecular networks responsible for the maintenance of primed pluripotency in human embryonic stem cells (hESCs) remain poorly defined. Wang et al. identify BCOR as a critical hESC regulator that defines a subtype of the PRC1.1 complexes with distinct recruitment and repression mechanisms that are essential for silencing differentiation programs in hESCs.",
keywords = "BCOR, human embryonic stem cells, pluripotency, polycomb repressive complexes",
author = "Zheng Wang and Gearhart, {Micah D} and Lee, {Yu Wei} and Ishan Kumar and Bulat Ramazanov and Yan Zhang and Charles Hernandez and Lu, {Alice Y.} and Nils Neuenkirchen and Jingjing Deng and Jiaqi Jin and Yuval Kluger and Neubert, {Thomas A.} and Bardwell, {Vivian J} and Ivanova, {Natalia B.}",
year = "2018",
month = "2",
day = "1",
doi = "10.1016/j.stem.2017.12.002",
language = "English (US)",
volume = "22",
pages = "235--251.e9",
journal = "Cell Stem Cell",
issn = "1934-5909",
publisher = "Cell Press",
number = "2",

}

TY - JOUR

T1 - A Non-canonical BCOR-PRC1.1 Complex Represses Differentiation Programs in Human ESCs

AU - Wang, Zheng

AU - Gearhart, Micah D

AU - Lee, Yu Wei

AU - Kumar, Ishan

AU - Ramazanov, Bulat

AU - Zhang, Yan

AU - Hernandez, Charles

AU - Lu, Alice Y.

AU - Neuenkirchen, Nils

AU - Deng, Jingjing

AU - Jin, Jiaqi

AU - Kluger, Yuval

AU - Neubert, Thomas A.

AU - Bardwell, Vivian J

AU - Ivanova, Natalia B.

PY - 2018/2/1

Y1 - 2018/2/1

N2 - Polycomb group proteins regulate self-renewal and differentiation in many stem cell systems. When assembled into two canonical complexes, PRC1 and PRC2, they sequentially deposit H3K27me3 and H2AK119ub histone marks and establish repressive chromatin, referred to as Polycomb domains. Non-canonical PRC1 complexes retain RING1/RNF2 E3-ubiquitin ligases but have unique sets of accessory subunits. How these non-canonical complexes recognize and regulate their gene targets remains poorly understood. Here, we show that the BCL6 co-repressor (BCOR), a member of the PRC1.1 complex, is critical for maintaining primed pluripotency in human embryonic stem cells (ESCs). BCOR depletion leads to the erosion of Polycomb domains at key developmental loci and the initiation of differentiation along endoderm and mesoderm lineages. The C terminus of BCOR regulates the assembly and targeting of the PRC1.1 complex, while the N terminus contributes to BCOR-PRC1.1 repressor function. Our findings advance understanding of Polycomb targeting and repression in ESCs and could apply broadly across developmental systems. Molecular networks responsible for the maintenance of primed pluripotency in human embryonic stem cells (hESCs) remain poorly defined. Wang et al. identify BCOR as a critical hESC regulator that defines a subtype of the PRC1.1 complexes with distinct recruitment and repression mechanisms that are essential for silencing differentiation programs in hESCs.

AB - Polycomb group proteins regulate self-renewal and differentiation in many stem cell systems. When assembled into two canonical complexes, PRC1 and PRC2, they sequentially deposit H3K27me3 and H2AK119ub histone marks and establish repressive chromatin, referred to as Polycomb domains. Non-canonical PRC1 complexes retain RING1/RNF2 E3-ubiquitin ligases but have unique sets of accessory subunits. How these non-canonical complexes recognize and regulate their gene targets remains poorly understood. Here, we show that the BCL6 co-repressor (BCOR), a member of the PRC1.1 complex, is critical for maintaining primed pluripotency in human embryonic stem cells (ESCs). BCOR depletion leads to the erosion of Polycomb domains at key developmental loci and the initiation of differentiation along endoderm and mesoderm lineages. The C terminus of BCOR regulates the assembly and targeting of the PRC1.1 complex, while the N terminus contributes to BCOR-PRC1.1 repressor function. Our findings advance understanding of Polycomb targeting and repression in ESCs and could apply broadly across developmental systems. Molecular networks responsible for the maintenance of primed pluripotency in human embryonic stem cells (hESCs) remain poorly defined. Wang et al. identify BCOR as a critical hESC regulator that defines a subtype of the PRC1.1 complexes with distinct recruitment and repression mechanisms that are essential for silencing differentiation programs in hESCs.

KW - BCOR

KW - human embryonic stem cells

KW - pluripotency

KW - polycomb repressive complexes

UR - http://www.scopus.com/inward/record.url?scp=85040446175&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85040446175&partnerID=8YFLogxK

U2 - 10.1016/j.stem.2017.12.002

DO - 10.1016/j.stem.2017.12.002

M3 - Article

VL - 22

SP - 235-251.e9

JO - Cell Stem Cell

T2 - Cell Stem Cell

JF - Cell Stem Cell

SN - 1934-5909

IS - 2

ER -