BAHCC1 binds H3K27me3 via a conserved BAH module to mediate gene silencing and oncogenesis

Fan, Huitao; Lu, Jiuwei; Guo, Yiran; Li, Dongxu; Zhang, Zhimin; Tsai, Yi-Hsuan; Pi, Wen‐Chieh; Ahn, Jeong Hyun; Gong, Weida; Yu, Xiang; Allison, David F.; Geng, Huimin; He, Shirley; Diao, Yarui; Chen, Wei Yi; Strahl, Brian D.; Cai, Ling; Song, Jikui; Wang, Gang Greg

doi:10.1038/s41588-020-00729-3

Cited by 72 publications

(58 citation statements)

References 80 publications

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“…RT-qPCR was carried out as previously described (17,26), with the primer sequence listed in Supplementary Table 6.…”

Section: Methodsmentioning

confidence: 99%

“…Beads were washed three times in NP40 lysis buffer, resuspended in 50 μl of 1× SDS sample buffer, and boiled at 90 degree for 5 min before loading onto SDS-PAGE gel. We conducted the biotinylated peptide pulldown using total cell lysate according to a previously described protocol (17,26).…”

Section: Methodsmentioning

confidence: 99%

“…A prevalent model for functional transduction of H3K27me3 in mammals is that H3K27me3 is read and bound by chromodomain harbored within the chromobox (CBX) component of canonical Polycomb repressive complex 1 (cPRC1), which can induce gene silencing at least partly through mono-ubiquitination of histone H2A lysine 119 (H2AK119ub1) (2,3,10,11) and/or a phase separation-mediated chromatin compaction mechanism (12–14). However, emerging evidence has shown that, in mammalian cells, H3K27me3 is also ‘sensed’ and bound by a second class of “reader” modules termed Bromo-Adjacent Homology (BAH), which exist within chromatin regulators such as BAH D omain Containing 1 (BAHD1) (15,16) and BAH and C oiled- c oil Domain-containing Protein 1 (BAHCC1) (17). In particular, it was recently demonstrated that disrupting the direct binding of the BAHCC1 BAH motif (BAHCC1 BAH ) to H3K27me3 via point mutagenesis leads to significant de-repression of the H3K27me3-demacated genes (17).…”

Section: Introductionmentioning

confidence: 99%

“…However, emerging evidence has shown that, in mammalian cells, H3K27me3 is also ‘sensed’ and bound by a second class of “reader” modules termed Bromo-Adjacent Homology (BAH), which exist within chromatin regulators such as BAH D omain Containing 1 (BAHD1) (15,16) and BAH and C oiled- c oil Domain-containing Protein 1 (BAHCC1) (17). In particular, it was recently demonstrated that disrupting the direct binding of the BAHCC1 BAH motif (BAHCC1 BAH ) to H3K27me3 via point mutagenesis leads to significant de-repression of the H3K27me3-demacated genes (17). Mechanistically, BAHCC1 interacts with histone deacetylases (HDACs), thereby linking H3K27me3 with histone deacetylation, an integral step of gene repression (17).…”

Section: Introductionmentioning

confidence: 99%

“…In particular, it was recently demonstrated that disrupting the direct binding of the BAHCC1 BAH motif (BAHCC1 BAH ) to H3K27me3 via point mutagenesis leads to significant de-repression of the H3K27me3-demacated genes (17). Mechanistically, BAHCC1 interacts with histone deacetylases (HDACs), thereby linking H3K27me3 with histone deacetylation, an integral step of gene repression (17). Interestingly, BAHD1 also interacts with HDACs and mediates heterochromatin formation in mammalian cells (15,18).…”

Section: Introductionmentioning

confidence: 99%

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A conserved BAH module within mammalian BAHD1 connects H3K27me3 to Polycomb gene silencing

Fan

Guo

Tsai

et al. 2021

Preprint

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Trimethylation of histone H3 lysine 27 (H3K27me3) is important for gene silencing and imprinting, (epi)genome organization and organismal development. In a prevalent model, the functional readout of H3K27me3 in mammalian cells is achieved through the H3K27me3-recognizing chromodomain harbored within the chromobox (CBX) component of canonical Polycomb repressive complex 1 (cPRC1), which induces chromatin compaction and gene repression. Here, we report that binding of H3K27me3 by a Bromo Adjacent Homology (BAH) domain harbored within BAH domain-containing protein 1 (BAHD1) is required for overall BAHD1 targeting to chromatin and for optimal repression of the H3K27me3-demarcated genes in mammalian cells. Disruption of direct interaction between BAHD1BAH and H3K27me3 by point mutagenesis leads to chromatin remodeling, notably, increased histone acetylation, at its Polycomb gene targets. Mice carrying an H3K27me3-interaction-defective mutation of Bahd1BAH causes marked embryonic lethality, showing a requirement of this pathway for normal development. Altogether, this work demonstrates an H3K27me3-initiated signaling cascade that operates through a conserved BAH 'reader' module within BAHD1 in mammals.

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“…RT-qPCR was carried out as previously described (17,26), with the primer sequence listed in Supplementary Table 6.…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

A conserved BAH module within mammalian BAHD1 connects H3K27me3 to Polycomb gene silencing

Fan

Guo

Tsai

et al. 2021

Preprint

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Infection by a helminth parasite is associated with changes in DNA methylation in the house sparrow

Lundregan

Mäkinen

Buer

et al. 2022

Ecology and Evolution

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Parasites can exert strong selective pressures on their hosts and influence the evolution of host immunity. While several studies have examined the genetic basis for parasite resistance, the role of epigenetics in the immune response to parasites is less understood. Yet, epigenetic modifications, such as changes in DNA methylation, may allow species to respond rapidly to parasite prevalence or virulence. To test the role of DNA methylation in relation to parasite infection, we examined genome‐wide DNA methylation before and during infection by a parasitic nematode, Syngamus trachea , in a natural population of house sparrows ( Passer domesticus ) using reduced representation bisulfite sequencing (RRBS). We found that DNA methylation levels were slightly lower in infected house sparrows, and we identified candidate genes relating to the initial immune response, activation of innate and adaptive immunity, and mucus membrane functional integrity that were differentially methylated between infected and control birds. Subsequently, we used methylation‐sensitive high‐resolution melting (MS‐HRM) analyses to verify the relationship between methylation proportion and S. trachea infection status at two candidate genes in a larger sample dataset. We found that methylation level at NR1D1 , but not CLDN22 , remained related to infection status and that juvenile recruitment probability was positively related to methylation level at NR1D1 . This underscores the importance of performing follow‐up studies on candidate genes. Our findings demonstrate that plasticity in the immune response to parasites can be epigenetically mediated and highlight the potential for epigenetic studies in natural populations to provide further mechanistic insight into host–parasite interactions.

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Rapid Single-Pot Assembly of Modular Chromatin Proteins for Epigenetic Engineering

Haynes

Priode

2022

Methods in Molecular Biology

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BAHCC1 binds H3K27me3 via a conserved BAH module to mediate gene silencing and oncogenesis

Cited by 72 publications

References 80 publications

A conserved BAH module within mammalian BAHD1 connects H3K27me3 to Polycomb gene silencing

A conserved BAH module within mammalian BAHD1 connects H3K27me3 to Polycomb gene silencing

Infection by a helminth parasite is associated with changes in DNA methylation in the house sparrow

Rapid Single-Pot Assembly of Modular Chromatin Proteins for Epigenetic Engineering

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