eames lecture 4

cartilage

sox9

bone

runx2

campomelic dysplaisa

sox9 heterozygous mutation

cleidocranial dysplasia

runx2 heterozygous mutation

transcription factors

runx2 and sox9

enhancer

short regulatory nt sequence

can be far away from gene, but always on same chromosome as gene

what binds to enhancers

transcription factors

what binds col2a1 enhancer near its gene

sox9

OG1, OG2, Col1a1, BSP, OPN

bone genes

has standard location of enhancers (enhancers always near promotor region)

runx2

non-standard location of enhancer

sox9

why does dna bend?

to bring enhancers and promotors closer to eachother and to coordinate multiple enhancers

dna bender

sox9

cytoskeleton of nucleus

fibrillar nuclear matrix

what serves a structrual role in organizing chromosomes and specific regions of nucleus?

fibrillar nuclear matrix

participates in transcriptional complex organized around nuclear matrix

runx2

binds and co-localizes with nuclear matrix proteins

runx2

hypothesis: ECM→integrin→cytoskeleton→nuclear matrix→____

runx2 activity

____ signalling increases runx2 activity by chemically modifying runx2

fgf

fgf→_____→runx2→increased transcriptional activity

ERK (phosphorylates and then acetylates)

_____ signalling increases binding of sox9 with Col2a1 enhancer (indirectly)

tgfB

when tgfB signalling occurs, what interacts with smad2/3?

sox9

smads associate with sox9 on ____

col2a1 enhancer

smads, phosphorylated by ____, gain the ability to interact with sox9

tgfB