WHSC1

This gene encodes a protein that contains four domains present in other developmental proteins: a PWWP domain, an HMG box, a SET domain, and a PHD-type zinc finger. It is expressed ubiquitously in early development. Wolf-Hirschhorn syndrome (WHS) is a malformation syndrome associated with a hemizygous deletion of the distal short arm of chromosome 4. This gene maps to the 165 kb WHS critical region and has also been involved in the chromosomal translocation t(4;14)(p16.3;q32.3) in multiple myelomas. Histone methyltransferase with histone H3 'Lys-27' (H3K27me) methyltransferase activity. Isoform 2 may act as a transcription regulator that binds DNA and suppresses IL5 transcription through HDAC recruitment.

wolf-hirschhorn syndrome candidate 1

Histone methyltransferase which specifically dimethylates nucleosomal histone H3 at 'Lys-36' (H3K36me2) (PubMed:27571355, PubMed:22099308, PubMed:19808676, PubMed:29728617, PubMed:33941880).
Also monomethylates nucleosomal histone H3 at 'Lys-36' (H3K36me) in vitro (PubMed:22099308).
Does not trimethylate nucleosomal histone H3 at 'Lys-36' (H3K36me3) (PubMed:22099308).
However, specifically trimethylates histone H3 at 'Lys-36' (H3K36me3) at euchromatic regions in embryonic stem (ES) cells (By similarity).
By methylating histone H3 at 'Lys-36', involved in the regulation of gene transcription during various biological processes (PubMed:16115125, PubMed:22099308, PubMed:29728617).
In ES cells, associates with developmental transcription factors such as SALL1 and represses inappropriate gene transcription mediated by histone deacetylation (By similarity).
During heart development, associates with transcription factor NKX2-5 to repress transcription of NKX2-5 target genes (By similarity).
Plays an essential role in adipogenesis, by regulating expression of genes involved in pre-adipocyte differentiation (PubMed:29728617).
During T-cell receptor (TCR) and CD28-mediated T-cell activation, promotes the transcription of transcription factor BCL6 which is required for follicular helper T (Tfh) cell differentiation (By similarity).
During B-cell development, required for the generation of the B1 lineage (By similarity).
During B2 cell activation, may contribute to the control of isotype class switch recombination (CRS), splenic germinal center formation, and the humoral immune response (By similarity).
Plays a role in class switch recombination of the immunoglobulin heavy chain (IgH) locus during B-cell activation (By similarity).
By regulating the methylation of histone H3 at 'Lys-36' and histone H4 at 'Lys-20' at the IgH locus, involved in TP53BP1 recruitment to the IgH switch region and promotes the transcription of IgA (By similarity).
Isoform 1
Histone methyltransferase which specifically dimethylates nucleosomal histone H3 at 'Lys-36' (H3K36me2).
Isoform 4
Histone methyltransferase which specifically dimethylates nucleosomal histone H3 at 'Lys-36' (H3K36me2) (PubMed:22099308).
Methylation of histone H3 at 'Lys-27' is controversial (PubMed:18172012, PubMed:22099308).
Mono-, di- or tri-methylates histone H3 at 'Lys-27' (H3K27me, H3K27me2 and H3K27me3) (PubMed:18172012).
Does not methylate histone H3 at 'Lys-27' (PubMed:22099308).
May act as a transcription regulator that binds DNA and suppresses IL5 transcription through HDAC recruitment (PubMed:11152655, PubMed:18172012).

Biological Process atrial septum primum morphogenesis Source:Ensembl
Biological Process atrial septum secundum morphogenesis Source:Ensembl
Biological Process bone development Source:Ensembl
Biological Process chromatin organization Source:UniProtKB-KW
Biological Process double-strand break repair Source:Reactome
Biological Process histone H3-K36 methylation Source:Ensembl
Biological Process histone H4-K20 methylation Source:Ensembl
Biological Process membranous septum morphogenesis Source:Ensembl
Biological Process negative regulation of transcription by RNA polymerase II Source:Ensembl
Biological Process positive regulation of isotype switching to IgA isotypes Source:Ensembl
Biological Process regulation of DNA-templated transcription Source:GO_Central1 Publication
Biological Process regulation of double-strand break repair via nonhomologous end joining Source:Ensembl
Biological Process regulation of establishment of protein localization Source:Ensembl

Nucleus
Chromosome
In embryonic stem (ES) cells, localizes to small foci, probably corresponding to euchromatin (By similarity).
In B-cells, localizes to Ig heavy chain switch region during class switch recombination (By similarity).
Isoform 1
Nucleus
Chromosome
Isoform 3
Nucleus
Isoform 4
Cytoplasm
Nucleus, nucleolus

Rauch-Steindl syndrome (RAUST):
An autosomal dominant disorder characterized by poor pre- and postnatal growth, facial dysmorphism, and variable developmental delay with delayed motor and speech acquisition and impaired intellectual. Other features may include hypotonia and behavioral abnormalities.