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Histone monoaminylation dynamics are regulated by a single enzyme and promote neural rhythmicity

ABSTRACT: Histone H3 monoaminylations at glutamine(Q) 5 represent an important family of epigenetic markers in neurons that play critical roles in the mediation of permissive gene expression (1, 2). We previously demonstrated that H3Q5 serotonylation(ser) and dopaminylation(dop) are catalyzed by the Transglutaminase 2 (TGM2) enzyme and alter both local and global chromatin states (3, 4). Here, we found that TGM2 additionally functions as an “eraser” of H3 monoaminylations that is capable of “rewriting” these epigenetic marks in cells, including a new class of this modification, H3Q5 histaminylation(his), which displays dynamic diurnal expression in brain and contributes to neural rhythmicity. We found that H3Q5his inhibits binding of the MLL1 complex to the H3 N-terminus and attenuates its methyltransferase activity on H3 lysine(K) 4. We determined that H3Q5 monoaminylation dynamics are dictated by local monoamine concentrations, which are utilized by TGM2. Taken together, we present here a novel mechanism through which a single chromatin regulatory enzyme is capable of sensing chemical microenvironments to affect the epigenetic states of cells.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Stephanie Stransky

LAB HEAD: Stephanie Stransky

PROVIDER: PXD053429 | Pride | 2024-10-10

REPOSITORIES: pride

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			Action	DRS
	Endogenouspeptide_WT_HistaminePlus.raw	Raw
	H3Q5his_MLL2_Replicate1.raw	Raw
	H3Q5his_MLL2_Replicate2.raw	Raw
	H3Q5his_MLL2_Replicate3.raw	Raw
	H3Q5his_MLL3_Replicate1.raw	Raw

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