Localization of the Drosophila pioneer factor GAF to subnuclear foci is driven by DNA binding and required to silence satellite repeat expression

Marissa M. Gaskill; Isabella V. Soluri; Annemarie E. Branks; Alan P. Boka; Michael R. Stadler; Katherine Vietor; Hao Yu S. Huang; Tyler J. Gibson; Apratim Mukherjee; Mustafa Mir; Shelby A. Blythe; Melissa M. Harrison

doi:10.1016/j.devcel.2023.06.010

Localization of the Drosophila pioneer factor GAF to subnuclear foci is driven by DNA binding and required to silence satellite repeat expression

Marissa M. Gaskill, Isabella V. Soluri, Annemarie E. Branks, Alan P. Boka, Michael R. Stadler, Katherine Vietor, Hao Yu S. Huang, Tyler J. Gibson, Apratim Mukherjee, Mustafa Mir, Shelby A. Blythe, Melissa M. Harrison^*

^*Corresponding author for this work

Molecular Biosciences

Research output: Contribution to journal › Article › peer-review

11 Scopus citations

Abstract

The eukaryotic genome is organized to enable the precise regulation of gene expression. This organization is established as the embryo transitions from a fertilized gamete to a totipotent zygote. To understand the factors and processes that drive genomic organization, we focused on the pioneer factor GAGA factor (GAF) that is required for early development in Drosophila. GAF transcriptionally activates the zygotic genome and is localized to subnuclear foci. This non-uniform distribution is driven by binding to highly abundant GA repeats. At GA repeats, GAF is necessary to form heterochromatin and silence transcription. Thus, GAF is required to establish both active and silent regions. We propose that foci formation enables GAF to have opposing transcriptional roles within a single nucleus. Our data support a model in which the subnuclear concentration of transcription factors acts to organize the nucleus into functionally distinct domains essential for the robust regulation of gene expression.

Original language	English (US)
Pages (from-to)	1610-1624.e8
Journal	Developmental Cell
Volume	58
Issue number	17
DOIs	https://doi.org/10.1016/j.devcel.2023.06.010
State	Published - Sep 11 2023

Funding

We thank Gary Karpen, Bloomington Drosophila Stock Center, and the Drosophila Genome Resource Center for providing reagents and fly lines. We acknowledge the University of Wisconsin-Madison Biochemistry Department Optical Core for access to microscopes and the University of Wisconsin-Madison Biotechnology Center and the NUSeq Core Facility for sequencing. Elizabeth Larson assisted with trouble-shooting the data analysis. M.M.G. and T.J.G. were supported by National Institutes of Health (NIH) T32 GM007215 . A.P.B. was supported by NIH T32 GM132039 . Experiments were supported by a NIH R35 GM136298 (M.M.H.), NIH DP2HD108775 (M.M.), and NIH R01HD101563 (S.A.B.). M.M.H. was also supported by a Vallee Scholar Award . M.M.H. is a Romnes Faculty Fellow and Vilas Faculty Mid-Career Investigator. M.M. was supported by a grant from Margaret Q Landenberger Foundation . S.A.B. is a Pew Scholar in the Biomedical Sciences. We thank Gary Karpen, Bloomington Drosophila Stock Center, and the Drosophila Genome Resource Center for providing reagents and fly lines. We acknowledge the University of Wisconsin-Madison Biochemistry Department Optical Core for access to microscopes and the University of Wisconsin-Madison Biotechnology Center and the NUSeq Core Facility for sequencing. Elizabeth Larson assisted with trouble-shooting the data analysis. M.M.G. and T.J.G. were supported by National Institutes of Health (NIH) T32 GM007215. A.P.B. was supported by NIH T32 GM132039. Experiments were supported by a NIH R35 GM136298 (M.M.H.), NIH DP2HD108775 (M.M.), and NIH R01HD101563 (S.A.B.). M.M.H. was also supported by a Vallee Scholar Award. M.M.H. is a Romnes Faculty Fellow and Vilas Faculty Mid-Career Investigator. M.M. was supported by a grant from Margaret Q Landenberger Foundation. S.A.B. is a Pew Scholar in the Biomedical Sciences. M.M.G. I.V.S. A.P.B. M.R.S. K.V. H.-Y.S.H. T.J.G. A.M. M.M. S.A.B. and M.M.H. performed the experiments and data analysis. M.M.G. and M.M.H. wrote the original draft. M.M.G. A.P.B. T.J.G. M.M. S.A.B. and M.M.H. revised and edited the manuscript. M.M. S.A.B. and M.M.H. acquired funding. The authors declare no competing interests. We support inclusive, diverse, and equitable conduct of research.

Keywords

Drosophila
MZT
ZGA
gene expression
heterochromatin
maternal-to-zygotic transition
subnuclear domains
zygotic genome acivation

ASJC Scopus subject areas

Molecular Biology
General Biochemistry, Genetics and Molecular Biology
Developmental Biology
Cell Biology

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Gaskill, M. M., Soluri, I. V., Branks, A. E., Boka, A. P., Stadler, M. R., Vietor, K., Huang, H. Y. S., Gibson, T. J., Mukherjee, A., Mir, M., Blythe, S. A., & Harrison, M. M. (2023). Localization of the Drosophila pioneer factor GAF to subnuclear foci is driven by DNA binding and required to silence satellite repeat expression. Developmental Cell, 58(17), 1610-1624.e8. https://doi.org/10.1016/j.devcel.2023.06.010

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abstract = "The eukaryotic genome is organized to enable the precise regulation of gene expression. This organization is established as the embryo transitions from a fertilized gamete to a totipotent zygote. To understand the factors and processes that drive genomic organization, we focused on the pioneer factor GAGA factor (GAF) that is required for early development in Drosophila. GAF transcriptionally activates the zygotic genome and is localized to subnuclear foci. This non-uniform distribution is driven by binding to highly abundant GA repeats. At GA repeats, GAF is necessary to form heterochromatin and silence transcription. Thus, GAF is required to establish both active and silent regions. We propose that foci formation enables GAF to have opposing transcriptional roles within a single nucleus. Our data support a model in which the subnuclear concentration of transcription factors acts to organize the nucleus into functionally distinct domains essential for the robust regulation of gene expression.",

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Gaskill, MM, Soluri, IV, Branks, AE, Boka, AP, Stadler, MR, Vietor, K, Huang, HYS, Gibson, TJ, Mukherjee, A, Mir, M, Blythe, SA & Harrison, MM 2023, 'Localization of the Drosophila pioneer factor GAF to subnuclear foci is driven by DNA binding and required to silence satellite repeat expression', Developmental Cell, vol. 58, no. 17, pp. 1610-1624.e8. https://doi.org/10.1016/j.devcel.2023.06.010

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T1 - Localization of the Drosophila pioneer factor GAF to subnuclear foci is driven by DNA binding and required to silence satellite repeat expression

AU - Gaskill, Marissa M.

AU - Soluri, Isabella V.

AU - Branks, Annemarie E.

AU - Boka, Alan P.

AU - Stadler, Michael R.

AU - Vietor, Katherine

AU - Huang, Hao Yu S.

AU - Gibson, Tyler J.

AU - Mukherjee, Apratim

AU - Mir, Mustafa

AU - Blythe, Shelby A.

AU - Harrison, Melissa M.

PY - 2023/9/11

Y1 - 2023/9/11

N2 - The eukaryotic genome is organized to enable the precise regulation of gene expression. This organization is established as the embryo transitions from a fertilized gamete to a totipotent zygote. To understand the factors and processes that drive genomic organization, we focused on the pioneer factor GAGA factor (GAF) that is required for early development in Drosophila. GAF transcriptionally activates the zygotic genome and is localized to subnuclear foci. This non-uniform distribution is driven by binding to highly abundant GA repeats. At GA repeats, GAF is necessary to form heterochromatin and silence transcription. Thus, GAF is required to establish both active and silent regions. We propose that foci formation enables GAF to have opposing transcriptional roles within a single nucleus. Our data support a model in which the subnuclear concentration of transcription factors acts to organize the nucleus into functionally distinct domains essential for the robust regulation of gene expression.

AB - The eukaryotic genome is organized to enable the precise regulation of gene expression. This organization is established as the embryo transitions from a fertilized gamete to a totipotent zygote. To understand the factors and processes that drive genomic organization, we focused on the pioneer factor GAGA factor (GAF) that is required for early development in Drosophila. GAF transcriptionally activates the zygotic genome and is localized to subnuclear foci. This non-uniform distribution is driven by binding to highly abundant GA repeats. At GA repeats, GAF is necessary to form heterochromatin and silence transcription. Thus, GAF is required to establish both active and silent regions. We propose that foci formation enables GAF to have opposing transcriptional roles within a single nucleus. Our data support a model in which the subnuclear concentration of transcription factors acts to organize the nucleus into functionally distinct domains essential for the robust regulation of gene expression.

KW - Drosophila

KW - MZT

KW - ZGA

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KW - heterochromatin

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KW - subnuclear domains

KW - zygotic genome acivation

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JF - Developmental Cell

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ER -

Localization of the Drosophila pioneer factor GAF to subnuclear foci is driven by DNA binding and required to silence satellite repeat expression

Abstract

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Keywords

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