ACD15, ACD21, and SLN regulate the accumulation and mobility of MBD6 to silence genes and transposable elements

Brandon A. Boone; Lucia Ichino; Shuya Wang; Jason Gardiner; Jaewon Yun; Yasaman Jami-Alahmadi; Jihui Sha; Cristy P. Mendoza; Bailey J. Steelman; Aliya van Aardenne; Sophia Kira-Lucas; Isabelle Trentchev; James A. Wohlschlegel; Steven E. Jacobsen

doi:10.1126/sciadv.adi9036

ACD15, ACD21, and SLN regulate the accumulation and mobility of MBD6 to silence genes and transposable elements

Brandon A. Boone, Lucia Ichino, Shuya Wang, Jason Gardiner, Jaewon Yun, Yasaman Jami-Alahmadi, Jihui Sha, Cristy P. Mendoza, Bailey J. Steelman, Aliya van Aardenne, Sophia Kira-Lucas, Isabelle Trentchev, James A. Wohlschlegel, Steven E. Jacobsen

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

Abstract

DNA methylation mediates silencing of transposable elements and genes in part via recruitment of the Arabidopsis MBD5/6 complex, which contains the methyl-CpG binding domain (MBD) proteins MBD5 and MBD6, and the J-domain containing protein SILENZIO (SLN). Here, we characterize two additional complex members: α-crystalline domain (ACD) containing proteins ACD15 and ACD21. We show that they are necessary for gene silencing, bridge SLN to the complex, and promote higher-order multimerization of MBD5/6 complexes within heterochromatin. These complexes are also highly dynamic, with the mobility of MBD5/6 complexes regulated by the activity of SLN. Using a dCas9 system, we demonstrate that tethering the ACDs to an ectopic site outside of heterochromatin can drive a massive accumulation of MBD5/6 complexes into large nuclear bodies. These results demonstrate that ACD15 and ACD21 are critical components of the gene-silencing MBD5/6 complex and act to drive the formation of higher-order, dynamic assemblies at CG methylation (meCG) sites.

Original language	English
Article number	eadi9036
Number of pages	14
Journal	Science advances
Volume	9
Issue number	46
DOIs	https://doi.org/10.1126/sciadv.adi9036
Publication status	Published - 17 Nov 2023
Externally published	Yes

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Boone, B. A., Ichino, L., Wang, S., Gardiner, J., Yun, J., Jami-Alahmadi, Y., Sha, J., Mendoza, C. P., Steelman, B. J., Aardenne, A. V., Kira-Lucas, S., Trentchev, I., Wohlschlegel, J. A., & Jacobsen, S. E. (2023). ACD15, ACD21, and SLN regulate the accumulation and mobility of MBD6 to silence genes and transposable elements. Science advances, 9(46), Article eadi9036. https://doi.org/10.1126/sciadv.adi9036

@article{5c166e127fcb4acd8b1f9fd9c511e7d7,

title = "ACD15, ACD21, and SLN regulate the accumulation and mobility of MBD6 to silence genes and transposable elements",

abstract = "DNA methylation mediates silencing of transposable elements and genes in part via recruitment of the Arabidopsis MBD5/6 complex, which contains the methyl-CpG binding domain (MBD) proteins MBD5 and MBD6, and the J-domain containing protein SILENZIO (SLN). Here, we characterize two additional complex members: α-crystalline domain (ACD) containing proteins ACD15 and ACD21. We show that they are necessary for gene silencing, bridge SLN to the complex, and promote higher-order multimerization of MBD5/6 complexes within heterochromatin. These complexes are also highly dynamic, with the mobility of MBD5/6 complexes regulated by the activity of SLN. Using a dCas9 system, we demonstrate that tethering the ACDs to an ectopic site outside of heterochromatin can drive a massive accumulation of MBD5/6 complexes into large nuclear bodies. These results demonstrate that ACD15 and ACD21 are critical components of the gene-silencing MBD5/6 complex and act to drive the formation of higher-order, dynamic assemblies at CG methylation (meCG) sites.",

author = "Boone, {Brandon A.} and Lucia Ichino and Shuya Wang and Jason Gardiner and Jaewon Yun and Yasaman Jami-Alahmadi and Jihui Sha and Mendoza, {Cristy P.} and Steelman, {Bailey J.} and Aardenne, {Aliya van} and Sophia Kira-Lucas and Isabelle Trentchev and Wohlschlegel, {James A.} and Jacobsen, {Steven E.}",

note = "Publisher Copyright: Copyright {\textcopyright} 2023 The Authors, some rights reserved.",

year = "2023",

month = nov,

day = "17",

doi = "10.1126/sciadv.adi9036",

language = "English",

volume = "9",

journal = "Science advances",

issn = "2375-2548",

publisher = "American Association for the Advancement of Science",

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Boone, BA, Ichino, L, Wang, S, Gardiner, J, Yun, J, Jami-Alahmadi, Y, Sha, J, Mendoza, CP, Steelman, BJ, Aardenne, AV, Kira-Lucas, S, Trentchev, I, Wohlschlegel, JA & Jacobsen, SE 2023, 'ACD15, ACD21, and SLN regulate the accumulation and mobility of MBD6 to silence genes and transposable elements', Science advances, vol. 9, no. 46, eadi9036. https://doi.org/10.1126/sciadv.adi9036

TY - JOUR

T1 - ACD15, ACD21, and SLN regulate the accumulation and mobility of MBD6 to silence genes and transposable elements

AU - Boone, Brandon A.

AU - Ichino, Lucia

AU - Wang, Shuya

AU - Gardiner, Jason

AU - Yun, Jaewon

AU - Jami-Alahmadi, Yasaman

AU - Sha, Jihui

AU - Mendoza, Cristy P.

AU - Steelman, Bailey J.

AU - Aardenne, Aliya van

AU - Kira-Lucas, Sophia

AU - Trentchev, Isabelle

AU - Wohlschlegel, James A.

AU - Jacobsen, Steven E.

PY - 2023/11/17

Y1 - 2023/11/17

N2 - DNA methylation mediates silencing of transposable elements and genes in part via recruitment of the Arabidopsis MBD5/6 complex, which contains the methyl-CpG binding domain (MBD) proteins MBD5 and MBD6, and the J-domain containing protein SILENZIO (SLN). Here, we characterize two additional complex members: α-crystalline domain (ACD) containing proteins ACD15 and ACD21. We show that they are necessary for gene silencing, bridge SLN to the complex, and promote higher-order multimerization of MBD5/6 complexes within heterochromatin. These complexes are also highly dynamic, with the mobility of MBD5/6 complexes regulated by the activity of SLN. Using a dCas9 system, we demonstrate that tethering the ACDs to an ectopic site outside of heterochromatin can drive a massive accumulation of MBD5/6 complexes into large nuclear bodies. These results demonstrate that ACD15 and ACD21 are critical components of the gene-silencing MBD5/6 complex and act to drive the formation of higher-order, dynamic assemblies at CG methylation (meCG) sites.

AB - DNA methylation mediates silencing of transposable elements and genes in part via recruitment of the Arabidopsis MBD5/6 complex, which contains the methyl-CpG binding domain (MBD) proteins MBD5 and MBD6, and the J-domain containing protein SILENZIO (SLN). Here, we characterize two additional complex members: α-crystalline domain (ACD) containing proteins ACD15 and ACD21. We show that they are necessary for gene silencing, bridge SLN to the complex, and promote higher-order multimerization of MBD5/6 complexes within heterochromatin. These complexes are also highly dynamic, with the mobility of MBD5/6 complexes regulated by the activity of SLN. Using a dCas9 system, we demonstrate that tethering the ACDs to an ectopic site outside of heterochromatin can drive a massive accumulation of MBD5/6 complexes into large nuclear bodies. These results demonstrate that ACD15 and ACD21 are critical components of the gene-silencing MBD5/6 complex and act to drive the formation of higher-order, dynamic assemblies at CG methylation (meCG) sites.

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U2 - 10.1126/sciadv.adi9036

DO - 10.1126/sciadv.adi9036

M3 - Article

SN - 2375-2548

VL - 9

JO - Science advances

JF - Science advances

IS - 46

M1 - eadi9036

ER -

ACD15, ACD21, and SLN regulate the accumulation and mobility of MBD6 to silence genes and transposable elements

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