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2017 ; 45
(3
): 1091-1104
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Reciprocal regulation of chromatin state and architecture by HOTAIRM1 contributes
to temporal collinear HOXA gene activation
#MMPMID28180285
Wang XQ
; Dostie J
Nucleic Acids Res
2017[Feb]; 45
(3
): 1091-1104
PMID28180285
show ga
Thousands of long non-coding RNAs (lncRNAs) have been identified in mammals, many
of which represent important regulators of gene expression. However, the
mechanisms used by lncRNAs to control transcription remain largely
uncharacterized. Here, we report on HOTAIRM1, a promising lncRNA biomarker in
leukemia and solid tumors. We find that HOTAIRM1 contributes to three-dimensional
chromatin organization changes required for the temporal collinear activation of
HOXA genes. We show that distinct HOTAIRM1 variants preferentially associate with
either UTX/MLL or PRC2 complexes to modulate the levels of activating and
silencing marks at the bivalent domain. HOTAIRM1 contributes to physical
dissociation of chromatin loops at the cluster proximal end, which delays
recruitment of the histone demethylase UTX and transcription of central HOXA
genes. Interestingly, we find overall proximal HOXA gene activation without
chromatin conformation changes by HOTAIRM1 in a different cell type. Our results
reveal a previously unappreciated relationship between chromatin structure,
architecture and lncRNA function.