Histone H3 lysine 36 methyltransferase Whsc1 promotes the association of Runx2 and p300 in the activation of bone-related genes.

[wolf-hirschhorn syndrome]

The orchestration of histone modifiers is required to establish the epigenomic status that regulates gene expression during development . Whsc 1 (Wolf -Hirschhorn Syndrome candidate 1 ), a histone H 3 lysine 36 (H 3 K 36 ) trimethyltransferase , is one of the major genes associated with Wolf -Hirshhorn syndrome , which is characterized by skeletal abnormalities . However , the role of Whsc 1 in skeletal development remains unclear . Here , we show that Whsc 1 regulates gene expression through Runt-related transcription factor (Runx ) 2 , a transcription factor central to bone development , and p 300 , a histone acetyltransferase , to promote bone differentiation . Whsc 1 -/- embryos exhibited defects in ossification in the occipital bone and sternum . Whsc 1 knockdown in pre-osteoblast cells perturbed histone modification patterns in bone -related genes and led to defects in bone differentiation . Whsc 1 increased the association of p 300 with Runx 2 , activating the bone -related genes Osteopontin (Opn ) and Collagen type Ia (Col 1 a 1 ), and Whsc 1 suppressed the overactivation of these genes via H 3 K 36 trimethylation . Our results suggest that Whsc 1 fine-tunes the expression of bone -related genes by acting as a modulator in balancing H 3 K 36 trimethylation and histone acetylation . Our results provide novel insight into the mechanisms by which this histone methyltransferase regulates gene expression .

Diseases
Validation

Diseases presenting "exhibited defects in ossification in the occipital bone" symptom

wolf-hirschhorn syndrome

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