The Role of Transcription Factors and Nuclear Pore Proteins in Controlling the Spatial Organization of the Yeast Genome

Donna Garvey Brickner; Carlo Randise-Hinchliff; Marine Lebrun Corbin; Julie Ming Liang; Stephanie Kim; Bethany Sump; Agustina D'Urso; Seo Hyun Kim; Atsushi Satomura; Heidi Schmit; Robert Coukos; Subin Hwang; Raven Watson; Jason H. Brickner

doi:10.1016/j.devcel.2019.05.023

The Role of Transcription Factors and Nuclear Pore Proteins in Controlling the Spatial Organization of the Yeast Genome

Donna Garvey Brickner, Carlo Randise-Hinchliff, Marine Lebrun Corbin, Julie Ming Liang, Stephanie Kim, Bethany Sump, Agustina D'Urso, Seo Hyun Kim, Atsushi Satomura, Heidi Schmit, Robert Coukos, Subin Hwang, Raven Watson, Jason H. Brickner^*

^*Corresponding author for this work

Molecular Biosciences

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

35 Scopus citations

Abstract

Loss of nuclear pore complex (NPC) proteins, transcription factors (TFs), histone modification enzymes, Mediator, and factors involved in mRNA export disrupts the physical interaction of chromosomal sites with NPCs. Conditional inactivation and ectopic tethering experiments support a direct role for the TFs Gcn4 and Nup2 in mediating interaction with the NPC but suggest an indirect role for factors involved in mRNA export or transcription. A conserved “positioning domain” within Gcn4 controls interaction with the NPC and inter-chromosomal clustering and promotes transcription of target genes. Such a function may be quite common; a comprehensive screen reveals that tethering of most yeast TFs is sufficient to promote targeting to the NPC. While some TFs require Nup100, others do not, suggesting two distinct targeting mechanisms. These results highlight an important and underappreciated function of TFs in controlling the spatial organization of the yeast genome through interaction with the NPC. Brickner et al. show that transcription factors (TFs) control positioning of genes through interaction with the nuclear pore complex. A “positioning domain” from one TF promotes interaction with the pore, and a global screen reveals that most yeast TFs mediate targeting to the NPC using at least two different pathways.

Original language	English (US)
Pages (from-to)	936-947.e4
Journal	Developmental Cell
Volume	49
Issue number	6
DOIs	https://doi.org/10.1016/j.devcel.2019.05.023
State	Published - Jun 17 2019

Funding

The authors thank members of the Brickner laboratory, Erik Andersen, and Alan Hinnebusch for helpful discussions and input. This work was supported by NIH R01 GM 080484 and R01 GM118712 (J.H.B.). A.D. was supported by NIH T32 GM008061; R.C. S.K. S.H.K. S.H. and R.W. were supported by Northwestern University undergraduate research fellowships. A.S. is supported by a JSPS Overseas postdoctoral fellowship from the Japanese Society for the Promotion of Science. Conceptualization, J.H.B. D.G.B. and C.R.H.; Methodology, D.G.B. C.R.H. and J.M.L.; Software and Formal Statistical Analysis, J.H.B. and A.S.; Investigation, D.G.B. C.R.H. M.L.C. J.M.L. S.K. B.S. A.D. S.H.K. H.S. R.C. S.H. and R.W.; Writing, J.H.B. D.G.B. and C.R.H.; Visualization, J.H.B. D.G.B. and C.R.H.; Supervision, J.H.B. and D.G.B.; Project Administration, J.H.B.; Funding Acquisition, J.H.B. The authors declare no competing interests. The authors thank members of the Brickner laboratory, Erik Andersen, and Alan Hinnebusch for helpful discussions and input. This work was supported by NIH R01 GM 080484 and R01 GM118712 (J.H.B.). A.D. was supported by NIH T32 GM008061 ; R.C., S.K., S.H.K., S.H., and R.W. were supported by Northwestern University undergraduate research fellowships. A.S. is supported by a JSPS Overseas postdoctoral fellowship from the Japanese Society for the Promotion of Science.

Keywords

chromatin
chromosome
inter-chromosomal clustering
nuclear architecture
nuclear pore complex
transcription

ASJC Scopus subject areas

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

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Brickner, D. G., Randise-Hinchliff, C., Corbin, M. L., Liang, J. M., Kim, S., Sump, B., D'Urso, A., Kim, S. H., Satomura, A., Schmit, H., Coukos, R., Hwang, S., Watson, R., & Brickner, J. H. (2019). The Role of Transcription Factors and Nuclear Pore Proteins in Controlling the Spatial Organization of the Yeast Genome. Developmental Cell, 49(6), 936-947.e4. https://doi.org/10.1016/j.devcel.2019.05.023

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title = "The Role of Transcription Factors and Nuclear Pore Proteins in Controlling the Spatial Organization of the Yeast Genome",

abstract = "Loss of nuclear pore complex (NPC) proteins, transcription factors (TFs), histone modification enzymes, Mediator, and factors involved in mRNA export disrupts the physical interaction of chromosomal sites with NPCs. Conditional inactivation and ectopic tethering experiments support a direct role for the TFs Gcn4 and Nup2 in mediating interaction with the NPC but suggest an indirect role for factors involved in mRNA export or transcription. A conserved “positioning domain” within Gcn4 controls interaction with the NPC and inter-chromosomal clustering and promotes transcription of target genes. Such a function may be quite common; a comprehensive screen reveals that tethering of most yeast TFs is sufficient to promote targeting to the NPC. While some TFs require Nup100, others do not, suggesting two distinct targeting mechanisms. These results highlight an important and underappreciated function of TFs in controlling the spatial organization of the yeast genome through interaction with the NPC. Brickner et al. show that transcription factors (TFs) control positioning of genes through interaction with the nuclear pore complex. A “positioning domain” from one TF promotes interaction with the pore, and a global screen reveals that most yeast TFs mediate targeting to the NPC using at least two different pathways.",

keywords = "chromatin, chromosome, inter-chromosomal clustering, nuclear architecture, nuclear pore complex, transcription",

author = "Brickner, {Donna Garvey} and Carlo Randise-Hinchliff and Corbin, {Marine Lebrun} and Liang, {Julie Ming} and Stephanie Kim and Bethany Sump and Agustina D'Urso and Kim, {Seo Hyun} and Atsushi Satomura and Heidi Schmit and Robert Coukos and Subin Hwang and Raven Watson and Brickner, {Jason H.}",

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day = "17",

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Brickner, DG, Randise-Hinchliff, C, Corbin, ML, Liang, JM, Kim, S, Sump, B, D'Urso, A, Kim, SH, Satomura, A, Schmit, H, Coukos, R, Hwang, S, Watson, R & Brickner, JH 2019, 'The Role of Transcription Factors and Nuclear Pore Proteins in Controlling the Spatial Organization of the Yeast Genome', Developmental Cell, vol. 49, no. 6, pp. 936-947.e4. https://doi.org/10.1016/j.devcel.2019.05.023

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T1 - The Role of Transcription Factors and Nuclear Pore Proteins in Controlling the Spatial Organization of the Yeast Genome

AU - Brickner, Donna Garvey

AU - Randise-Hinchliff, Carlo

AU - Corbin, Marine Lebrun

AU - Liang, Julie Ming

AU - Kim, Stephanie

AU - Sump, Bethany

AU - D'Urso, Agustina

AU - Kim, Seo Hyun

AU - Satomura, Atsushi

AU - Schmit, Heidi

AU - Coukos, Robert

AU - Hwang, Subin

AU - Watson, Raven

AU - Brickner, Jason H.

PY - 2019/6/17

Y1 - 2019/6/17

N2 - Loss of nuclear pore complex (NPC) proteins, transcription factors (TFs), histone modification enzymes, Mediator, and factors involved in mRNA export disrupts the physical interaction of chromosomal sites with NPCs. Conditional inactivation and ectopic tethering experiments support a direct role for the TFs Gcn4 and Nup2 in mediating interaction with the NPC but suggest an indirect role for factors involved in mRNA export or transcription. A conserved “positioning domain” within Gcn4 controls interaction with the NPC and inter-chromosomal clustering and promotes transcription of target genes. Such a function may be quite common; a comprehensive screen reveals that tethering of most yeast TFs is sufficient to promote targeting to the NPC. While some TFs require Nup100, others do not, suggesting two distinct targeting mechanisms. These results highlight an important and underappreciated function of TFs in controlling the spatial organization of the yeast genome through interaction with the NPC. Brickner et al. show that transcription factors (TFs) control positioning of genes through interaction with the nuclear pore complex. A “positioning domain” from one TF promotes interaction with the pore, and a global screen reveals that most yeast TFs mediate targeting to the NPC using at least two different pathways.

AB - Loss of nuclear pore complex (NPC) proteins, transcription factors (TFs), histone modification enzymes, Mediator, and factors involved in mRNA export disrupts the physical interaction of chromosomal sites with NPCs. Conditional inactivation and ectopic tethering experiments support a direct role for the TFs Gcn4 and Nup2 in mediating interaction with the NPC but suggest an indirect role for factors involved in mRNA export or transcription. A conserved “positioning domain” within Gcn4 controls interaction with the NPC and inter-chromosomal clustering and promotes transcription of target genes. Such a function may be quite common; a comprehensive screen reveals that tethering of most yeast TFs is sufficient to promote targeting to the NPC. While some TFs require Nup100, others do not, suggesting two distinct targeting mechanisms. These results highlight an important and underappreciated function of TFs in controlling the spatial organization of the yeast genome through interaction with the NPC. Brickner et al. show that transcription factors (TFs) control positioning of genes through interaction with the nuclear pore complex. A “positioning domain” from one TF promotes interaction with the pore, and a global screen reveals that most yeast TFs mediate targeting to the NPC using at least two different pathways.

KW - chromatin

KW - chromosome

KW - inter-chromosomal clustering

KW - nuclear architecture

KW - nuclear pore complex

KW - transcription

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SN - 1534-5807

VL - 49

SP - 936-947.e4

JO - Developmental Cell

JF - Developmental Cell

IS - 6

ER -

The Role of Transcription Factors and Nuclear Pore Proteins in Controlling the Spatial Organization of the Yeast Genome

Abstract

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Keywords

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