
cBAF複合体は、ポリコーム関連ヒストン修飾H3K27me3とH2AK119ubを効果的に除去し、Nkx2.9遺伝子の転写を活性化する。一方、gBAFとpBAF複合体はこれらのポリコーム修飾を十分に除去できない。


coremsg

Chromatin regulators are a group of proteins that can alter the physical properties of chromatin to make it more or less permissive to transcription by modulating another protein’s access to a specific DNA sequence through changes in nucleosome occupancy or histone modifications at a particular locus. Mammalian SWI/SNF complexes (mSWI/SNF) are a group of ATPase-dependent chromatin remodelers that alter chromatin states. In mouse embryonic stem cells (mESCs), there are three primary forms of mSWI/SNF: canonical BAF (cBAF), polybromo-associated BAF (pBAF), and GLTSCR-associated BAF (gBAF or ncBAF). While cBAF and gBAF contain the SS18 protein subunit, pBAF lacks SS18. Previous studies used a novel dCas9-mediated inducible recruitment (FIRE-Cas9) of mSWI/SNF complexes via SS18 to the Nkx2.9 locus. Nkx2.9 is a developmentally regulated gene that requires mSWI/SNF for transcriptional activation during neural differentiation. However, in mESCs, Nkx2.9 is bivalent, meaning nucleosomes at the locus have both active and polycomb-associated repressive modifications. Upon recruitment of SS18-containing complexes, polycomb-associated histone marks are removed, followed by transcriptional activation of Nkx2.9 . However, since both cBAF and gBAF share the SS18 subunit, it is unclear whether one or both complexes oppose the polycomb repressive marks. The ability of pBAF to do the same also remains unknown. In this study, we used unique subunits to recruit each of the three complexes to the Nkx2.9 locus individually. Here, we show that cBAF most effectively opposes polycomb repressive marks at Nkx2.9 , leading to transcriptional activation of the gene. Recruitment of cBAF complexes leads to a significant loss of the polycomb repressive-2 H3K27me3 and polycomb repressive-1 H2AK119ub histone marks, whereas gBAF and pBAF do not. Moreover, nucleosome occupancy alone cannot explain the loss of these marks. Our results demonstrate that cBAF has a unique role in the direct opposition of polycomb-associated histone modifications that gBAF and pBAF do not share.

1.  Cell Cycle and Cancer Biology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, 73104

2.  Department of Cell Biology, University of Oklahoma Health Science Center, Oklahoma City, OK, 73104

### Competing Interest Statement

The authors have declared no competing interest.

Differential Modulation of Polycomb-Associated Histone Marks by cBAF, pBAF, and gBAF Complexes

マウス胚性幹細胞におけるcbaf-pbaf-gbaf複合体によるポリコーム関連ヒストン修飾の差異的な調節


マウス胚性幹細胞におけるcBAF、pBAF、gBAF複合体によるポリコーム関連ヒストン修飾の差異的な調節


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H1ヒストンは、RNA 指向性 DNA メチル化経路の異染色質への浸入を制限することで、ゲノムの機能的な区分を維持する。


Silencing pathways prevent transposable element (TE) proliferation and help to maintain genome integrity through cell division. Silenced genomic regions can be classified as either euchromatic or heterochromatic, and are targeted by genetically separable epigenetic pathways. In plants, the RNA-directed DNA methylation (RdDM) pathway targets mostly euchromatic regions, while CMT DNA methyltransferases are mainly associated with heterochromatin. However, many epigenetic features - including DNA methylation patterning - are largely indistinguishable between these regions, so how the functional separation is maintained is unclear. The linker histone H1 is preferentially localized to heterochromatin and has been proposed to restrict RdDM from encroachment. To test this hypothesis, we followed RdDM genomic localization in an h1 mutant by performing ChIP-seq on the largest subunit, NRPE1, of the central RdDM polymerase, Pol V. Loss of H1 resulted in NRPE1 enrichment predominantly in heterochromatic TEs. Increased NRPE1 binding was associated with increased chromatin accessibility in h1 , suggesting that H1 restricts NRPE1 occupancy by compacting chromatin. However, RdDM occupancy did not impact H1 localization, demonstrating that H1 hierarchically restricts RdDM positioning. H1 mutants experience major symmetric (CG and CHG) DNA methylation gains, and by generating an h1/nrpe1 double mutant, we demonstrate these gains are largely independent of RdDM. However, loss of NRPE1 occupancy from a subset of euchromatic regions in h1 corresponded to loss of methylation in all sequence contexts, while at ectopically bound heterochromatic loci, NRPE1 deposition correlated with increased methylation specifically in the CHH context. Additionally, we found that H1 similarly restricts the occupancy of the methylation reader, SUVH1, and polycomb-mediated H3K27me3. Together, the results support a model whereby H1 helps maintain the exclusivity of heterochromatin by preventing encroachment from other competing pathways.

### Competing Interest Statement

The authors have declared no competing interest.

H1 restricts euchromatin-associated methylation pathways from heterochromatic encroachment

h1ヒストンが異染色質への-rna-指向性-dna-メチル化経路の浸入を制限する


H1ヒストンが異染色質への RNA 指向性 DNA メチル化経路の浸入を制限する



マラリア原虫 Plasmodium falciparum の MORC タンパク質は、様々な転写因子や染色質リモデリング因子と相互作用し、特に多様な抗原遺伝子群の発現制御に関与している。


Dynamic control of gene expression is critical for blood stage development of malaria parasites. Here, we used multi-omic analyses to investigate transcriptional regulation by the chromatin-associated microrchidia protein, MORC, during asexual blood stage development of the human malaria parasite Plasmodium falciparum . We show that Pf MORC (PF3D7\_1468100) interacts with a suite of nuclear proteins, including APETALA2 (AP2) transcription factors ( Pf AP2-G5, Pf AP2-O5, Pf AP2-I, PF3D7\_0420300, PF3D7\_0613800, PF3D7\_1107800, and PF3D7\_1239200), a DNA helicase DS60 (PF3D7\_1227100), and other chromatin remodelers ( Pf CHD1 and Pf EELM2). Transcriptomic analysis of Pf MORCHA-glmS knockdown parasites revealed 163 differentially expressed genes belonging to hypervariable multigene families, along with upregulation of genes mostly involved in host cell invasion. In vivo genome-wide chromatin occupancy analysis during both trophozoite and schizont stages of development demonstrates that Pf MORC is recruited to repressed, multigene families, including the var genes in subtelomeric chromosomal regions. Collectively, we find that Pf MORC is found in chromatin complexes that play a role in the epigenetic control of asexual blood stage transcriptional regulation and chromatin organization.

### Competing Interest Statement

The authors have declared no competing interest.

A Plasmodium falciparum MORC protein complex modulates epigenetic control of gene expression through interaction with heterochromatin

マラリア原虫-plasmodium-falciparum-の-morc-タンパク質は異染色質との相互作用を通じて遺伝子発現を調節する


マラリア原虫 Plasmodium falciparum の MORC タンパク質は異染色質との相互作用を通じて遺伝子発現を調節する
