MBTD1

MBTD1 (Mbt Domain Containing 1) is a Protein Coding gene. Diseases associated with MBTD1 include Endometrial Stromal Sarcoma and Endometrial Stromal Nodule. Among its related pathways are Mesodermal Commitment Pathway. An important paralog of this gene is L3MBTL2.

Full Name

MBT DOMAIN CONTAINING 1

Function

Chromatin reader component of the NuA4 histone acetyltransferase complex, a multiprotein complex involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A (PubMed:27153538, PubMed:32209463).

The NuA4 complex plays a direct role in repair of DNA double-strand breaks (DSBs) by promoting homologous recombination (HR) (PubMed:27153538).

MBTD1 specifically recognizes and binds monomethylated and dimethylated 'Lys-20' on histone H4 (H4K20me1 and H4K20me2, respectively) (PubMed:19841675, PubMed:27153538, PubMed:32209463).

In the NuA4 complex, MBTD1 promotes recruitment of the complex to H4K20me marks by competing with TP53BP1 for binding to H4K20me (PubMed:27153538).

Following recruitment to H4K20me at DNA breaks, the NuA4 complex catalyzes acetylation of 'Lys-15' on histone H2A (H2AK15), blocking the ubiquitination mark required for TP53BP1 localization at DNA breaks, thereby promoting homologous recombination (HR) (PubMed:27153538).

Biological Process

Chromatin organization Source: UniProtKB-KW
Double-strand break repair via homologous recombination Source: UniProtKB
Embryonic skeletal system development Source: Ensembl
Histone acetylation Source: ComplexPortal
Histone H2A acetylation Source: ComplexPortal
Histone H4 acetylation Source: ComplexPortal
Negative regulation of transcription, DNA-templated Source: GO_Central
Positive regulation of double-strand break repair via homologous recombination Source: ComplexPortal
Positive regulation of transcription, DNA-templated Source: ComplexPortal
Regulation of apoptotic process Source: ComplexPortal
Regulation of cell cycle Source: ComplexPortal
Regulation of double-strand break repair Source: ComplexPortal

Cellular Location

Nucleus
Other locations
Chromosome

Involvement in disease

A chromosomal aberration involving MBTD1 is a cause of acute poorly differentiated myeloid leukemia. Translocation (10;17)(p15;q21) with ZMYND11.