학술논문

A non-canonical BRD9-containing BAF chromatin remodeling complex regulates naive pluripotency in mouse embryonic stem cells
Document Type
article
Source
Nature Communications. 9(1)
Subject
Biochemistry and Cell Biology
Biological Sciences
Stem Cell Research
Human Genome
Regenerative Medicine
Genetics
Stem Cell Research - Embryonic - Non-Human
1.1 Normal biological development and functioning
Underpinning research
Generic health relevance
Animals
Cell Proliferation
Cells
Cultured
Chromosomal Proteins
Non-Histone
Gene Expression Regulation
Gene Regulatory Networks
HCT116 Cells
HEK293 Cells
Humans
Mice
Mice
Knockout
Mouse Embryonic Stem Cells
Pluripotent Stem Cells
RNA Interference
Transcription Factors
Language
Abstract
The role of individual subunits in the targeting and function of the mammalian BRG1-associated factors (BAF) complex in embryonic stem cell (ESC) pluripotency maintenance has not yet been elucidated. Here we find that the Bromodomain containing protein 9 (BRD9) and Glioma tumor suppressor candidate region gene 1 (GLTSCR1) or its paralog GLTSCR1-like (GLTSCR1L) define a smaller, non-canonical BAF complex (GBAF complex) in mouse ESCs that is distinct from the canonical ESC BAF complex (esBAF). GBAF and esBAF complexes are targeted to different genomic features, with GBAF co-localizing with key regulators of naive pluripotency, which is consistent with its specific function in maintaining naive pluripotency gene expression. BRD9 interacts with BRD4 in a bromodomain-dependent fashion, which leads to the recruitment of GBAF complexes to chromatin, explaining the functional similarity between these epigenetic regulators. Together, our results highlight the biological importance of BAF complex heterogeneity in maintaining the transcriptional network of pluripotency.