Interplay of BAF and MLL4 promotes cell type-specific enhancer activation

Autor: Young-Kwon Park, Zhijiang Yan, Weiqun Peng, Ji-Eun Lee, Weidong Wang, Kai Ge, Tommy O'Haren, Kaitlin McKernan
Rok vydání: 2020
Předmět:
0301 basic medicine
Cell biology
Science
Cellular differentiation
Cell
General Physics and Astronomy
Development
Article
General Biochemistry
Genetics and Molecular Biology
Chromatin remodeling
Histones
Mice
03 medical and health sciences
0302 clinical medicine
medicine
Animals
Promoter Regions
Genetic
Enhancer
Transcription factor
Adipogenesis
Multidisciplinary
biology
Chemistry
DNA Helicases
Nuclear Proteins
Cell Differentiation
Histone-Lysine N-Methyltransferase
SMARCB1 Protein
General Chemistry
Chromatin Assembly and Disassembly
Chromatin
Gene regulation
DNA-Binding Proteins
Enhancer Elements
Genetic
030104 developmental biology
medicine.anatomical_structure
Histone
Gene Expression Regulation
SMARCA4
biology.protein
Epigenetics
Gene expression
030217 neurology & neurosurgery
Transcription Factors
Zdroj: Nature Communications
Nature Communications, Vol 12, Iss 1, Pp 1-16 (2021)
DOI: 10.1101/2020.06.24.168146
Popis: Cell type-specific enhancers are activated by coordinated actions of lineage-determining transcription factors (LDTFs) and chromatin regulators. The SWI/SNF chromatin remodeling complex BAF and the histone H3K4 methyltransferase MLL4 (KMT2D) are both implicated in enhancer activation. However, the interplay between BAF and MLL4 in enhancer activation remains unclear. Using adipogenesis as a model system, we identify BAF as the major SWI/SNF complex that colocalizes with MLL4 and LDTFs on active enhancers and is required for cell differentiation. In contrast, the promoter enriched SWI/SNF complex PBAF is dispensable for adipogenesis. By depleting BAF subunits SMARCA4 (BRG1) and SMARCB1 (SNF5) as well as MLL4 in cells, we show that BAF and MLL4 reciprocally regulate each other’s binding on active enhancers before and during adipogenesis. By focusing on enhancer activation by the adipogenic pioneer transcription factor C/EBPβ without inducing cell differentiation, we provide direct evidence for an interdependent relationship between BAF and MLL4 in activating cell type-specific enhancers. Together, these findings reveal a positive feedback between BAF and MLL4 in promoting LDTF-dependent activation of cell type-specific enhancers.
The SWI/SNF complex BAF and the histone H3K4 methyltransferase MLL4 (KMT2D) play critical roles in enhancer activation, however the interplay between them has remained unclear. Here the authors show that BAF and MLL4 are interdependent in promoting enhancer activation by lineage-determining transcription factors during adipogenesis.
Databáze: OpenAIRE
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