Human histone acetyltransferase 1 protein preferentially acetylates H4 histone molecules in H3.1-H4 over H3.3-H4.
In mammalian cells, canonical histone H3 (H3.1) and H3 variant (H3.3) differ by five amino acids and are assembled, along with histone H4, into nucleosomes via distinct nucleosome assembly pathways. H3.1-H4 molecules are assembled by histone chaperone CAF-1 in a replication-coupled process, whereas H3.3-H4 are assembled via HIRA in a replication-independent pathway. Newly synthesized histone H4 is acetylated at lysine 5 and 12 (H4K5,12) by histone acetyltransferase 1 (HAT1). However, it remains unclear whether HAT1 and H4K5,12ac differentially regulate these two nucleosome assembly processes. Here, we show that HAT1 binds and acetylates H4 in H3.1-H4 molecules preferentially over H4 in H3.3-H4. Depletion of Hat1, the catalytic subunit of HAT1 complex, results in reduced H3.1 occupancy at H3.1-enriched genes and reduced association of Importin 4 with H3.1, but not H3.3. Finally, depletion of Hat1 or CAF-1p150 leads to changes in expression of a H3.1-enriched gene. These results indicate that HAT1 differentially impacts nucleosome assembly of H3.1-H4 and H3.3-H4.
Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota 55905, USA.
Hui
H
Zhang
Junhong
J
Han
Bin
B
Kang
Rebecca
R
Burgess
Zhiguo
Z
Zhang
D000107:Acetylation; D021581:Active Transport, Cell Nucleus / Q000502:physiology; D056504:Chromatin Assembly Factor-1 / Q000378:metabolism; D004261:DNA Replication / Q000502:physiology; D057809:HEK293 Cells; D006367:HeLa Cells; D051548:Histone Acetyltransferases / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D026901:Membrane Transport Proteins / Q000378:metabolism; D009707:Nucleosomes / Q000378:metabolism*; D016196:S Phase / Q000502:physiology; D013379:Substrate Specificity / Q000502:physiology; D014157:Transcription Factors
C489780:CNOT8 protein, human; D056504:Chromatin Assembly Factor-1; D006657:Histones; C545055:IPO4 protein, human; D026901:Membrane Transport Proteins; D009707:Nucleosomes; D014157:Transcription Factors; D051548:Histone Acetyltransferases; C110880:histone acetyltransferase type B complex